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      Association Between Breastfeeding and Postpartum Multiple Sclerosis Relapses : A Systematic Review and Meta-analysis

      research-article
      , MD, MAS 1 , , , DO, MSc 1 , , MD, PhD, MAS 1 , 2 , , PhD, MS 3 , , MD, PhD 1
      JAMA Neurology
      American Medical Association

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          Key Points

          Question

          Is breastfeeding associated with reduction in postpartum relapses in women with multiple sclerosis?

          Findings

          In this systematic review and meta-analysis of 24 studies that include 2974 women, there was a reduced rate of postpartum multiple sclerosis relapses in women who were breastfeeding compared with those who were not breastfeeding, with a stronger benefit of exclusive rather than nonexclusive breastfeeding. Compared with nonbreastfeeding, breastfeeding was associated with a 43% lower rate of postpartum relapse, although it is not possible to exclude residual confounding.

          Meaning

          Breastfeeding appears to be protective against postpartum multiple sclerosis relapses, although additional high-quality prospective studies appear to be needed.

          Abstract

          Importance

          Multiple sclerosis (MS) relapses may be increased in the postpartum period, and whether breastfeeding is associated with reduction in the risk of postpartum relapses remains controversial.

          Objective

          To perform a systematic review and meta-analysis to evaluate whether breastfeeding is associated with reduction in postpartum MS relapses compared with not breastfeeding.

          Data Sources

          PubMed and Embase were searched for studies assessing the association between breastfeeding and MS disease activity published between January 1, 1980, and July 11, 2018, as well as reference lists of selected articles.

          Study Selection

          All study designs assessing the association between breastfeeding and postpartum relapses in MS relative to a comparator group were included.

          Data Extraction and Synthesis

          Study eligibility assessment and extraction of study characteristics, methods, and outcomes, were performed independently by 2 reviewers following PRISMA guidelines. Risk of bias was evaluated by 2 independent reviewers with the ROBINS-I tool for nonrandomized, interventional studies. Findings from studies with data available for the number of women with postpartum relapses in the breastfeeding and nonbreastfeeding groups were combined with a random-effects model.

          Main Outcomes and Measures

          Postpartum MS relapse.

          Results

          The search identified 462 unique citations, and 24 (2974 women) satisfied eligibility criteria and were included, of which 16 were included in the quantitative meta-analysis. The pooled summary odds ratio for the association of breastfeeding with postpartum relapses was 0.63 (95% CI, 0.45-0.88; P = .006) compared with a reference of nonbreastfeeding. Pooled adjusted hazard ratio across 4 studies that reported this finding was 0.57 (95% CI, 0.38-0.85; P = .006). There was moderate heterogeneity ( I 2 = 48%), which was explained by variable prepregnancy relapse rate, postpartum follow-up duration, and the publication year. A stronger association was seen in studies of exclusive rather than nonexclusive breastfeeding, although both demonstrated an association. Studies were rated at moderate and serious risk of bias, with concern for residual confounding, although sensitivity analysis including only moderate quality studies was consistent with a protective outcome of breastfeeding.

          Conclusions and Relevance

          These findings suggest that breastfeeding is protective against postpartum relapses in MS, although high-quality prospective studies to date are limited and well-designed observational studies that aim to emulate a randomized trial would be of benefit.

          Abstract

          This systematic review and meta-analysis examines the occurrence of multiple sclerosis relapses in women who are breastfeeding

          Related collections

          Most cited references27

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          • Abstract: found
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          Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse.

          The influence of pregnancy in multiple sclerosis has been a matter of controversy for a long time. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed to assess the possible influence of pregnancy and delivery on the clinical course of multiple sclerosis. We report here the 2-year post-partum follow-up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery. The relapse rate in each trimester up to the end of the second year post-partum was compared with that in the pre-pregnancy year. Clinical predictors of the presence or absence of a post-partum relapse were analysed by logistic regression analysis. Using the best multivariate model, women were classified as having or not having a post-partum relapse predicted, and this was compared with the observed outcome. The results showed that, compared with the pre-pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery. Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre-pregnancy year. Despite the increased risk for the 3 months post-partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period. Three indices, an increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke's Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post-partum relapse. Neither epidural analgesia nor breast-feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model. In conclusion, the results for the second year post-partum confirm that the relapse rate remains similar to that of the pre-pregnancy year, after an increase in the first trimester following delivery. Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post- partum 3 months. This is, however, not sufficient to identify in advance women with multiple sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post-partum relapses.
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            • Record: found
            • Abstract: not found
            • Article: not found

            Predictors and dynamics of postpartum relapses in women with multiple sclerosis

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              • Record: found
              • Abstract: found
              • Article: not found

              Exclusive Breastfeeding and the Effect on Postpartum Multiple Sclerosis Relapses.

              Women with multiple sclerosis (MS) experience an elevated risk of relapse after giving birth. The effect of exclusive breastfeeding on postpartum risk of MS relapse is unclear.
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                Author and article information

                Journal
                JAMA Neurol
                JAMA Neurol
                JAMA Neurol
                JAMA Neurology
                American Medical Association
                2168-6149
                2168-6157
                March 2020
                9 December 2019
                9 December 2020
                : 77
                : 3
                : 327-338
                Affiliations
                [1 ]UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco
                [2 ]Department of Neurology, University of California, San Diego
                [3 ]Preventive & Restorative Dental Sciences, University of California, San Francisco
                Author notes
                Article Information
                Accepted for Publication: October 11, 2019.
                Corresponding Author: Kristen M. Krysko, MD, MAS, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Ln, Ste 221, San Francisco, CA 94158 ( kristen.krysko@ 123456mail.utoronto.ca ).
                Published Online: December 9, 2019. doi:10.1001/jamaneurol.2019.4173
                Author Contributions: Drs Krysko and Waubant had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Krysko, Graves, Lazar, Waubant.
                Acquisition, analysis, or interpretation of data: Krysko, Rutatangwa, Lazar, Waubant.
                Drafting of the manuscript: Krysko.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Krysko.
                Administrative, technical, or material support: Krysko.
                Supervision: Graves, Lazar, Waubant.
                Conflict of Interest Disclosures: Dr Krysko reported receiving grants from the National Multiple Sclerosis Society and Biogen, Idec during the conduct of the study outside the submitted work and is funded by a Sylvia Lawry Physician Fellowship through the National Multiple Sclerosis Society (FP-1605-08753; PI Krysko). Dr Graves reported receiving personal speaking and consulting fees from Novartis, Celgene, and Genzyme Sanofi, and grants from Biogen outside the submitted work. No other disclosures were reported.
                Funding/Support: This investigation was supported by a Sylvia Lawry Physician Fellowship from the National Multiple Sclerosis Society (FP-1605-08753; PI Krysko).
                Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: Evans Whitaker, MD MLIS (University of California, San Francisco), assisted with the literature search process. Annette Langer-Gould, MD, PhD (Department of Research & Evaluation, Kaiser Permanente Southern California), and Kerstin Hellwig, MD (Department of Neurology, St Josef Hospital, Ruhr-University Bochum), who are experts in the field, reviewed the list of included studies for completeness. We thank the authors of the included studies who provided additional information as requested: Nora Fernández Liguori, MD (Department of Neurology, Hospital Enrique Tornu), Kerstin Hellwig, MD (Department of Neurology, St Josef Hospital, Ruhr-University Bochum), Annette Langer-Gould MD, PhD (Department of Research & Evaluation, Kaiser Permanente Southern California), Tessel Runia, MD PhD (Department of Neurology, Erasmus MC), Emilio Portaccio, MD (Struttura Complessa Neurologia-Firenze, AUSL Toscana Centro), Maria Pia Amato, MD (Department of Neurology, University of Florence & Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Don Carlo Gnocchi). These individuals did not receive compensation for their contributions.
                Article
                PMC6902174 PMC6902174 6902174 noi190096
                10.1001/jamaneurol.2019.4173
                6902174
                31816024
                69e56f5d-e24e-4485-ac23-cc9e8a9a238f
                Copyright 2019 American Medical Association. All Rights Reserved.
                History
                : 17 July 2019
                : 11 October 2019
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                Research
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