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Association Between Breastfeeding and Postpartum Multiple Sclerosis RelapsesA Systematic Review and Meta-analysis

Educational Objective
To investigate whether breastfeeding is associated with a reduction in postpartum relapses in women with multiple sclerosis (MS).
1 Credit CME
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 (I2 = 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.

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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@mail.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.

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