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Breastfeeding and risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

INTRODUCTION
The causes of multiple sclerosis (MS) are not fully understood, yet. Genetic predisposition, environmental and lifestyle factors as well as an interplay thereof constitute relevant factors in the development of MS. Especially early-life risk factors such as having been breastfed may also be of relevance. Breast milk provides the new-born not only with essential nutrients and vitamins but also with numerous immune-active molecules, metabolites, oligosaccharides and microbial components that are important for the development of the immune system. We present a systematic review and meta-analysis on the influence of having been breastfed during infancy on the risk of developing MS.


METHODS
The databases MEDLINE, Cochrane Library and Web of Science were systematically searched for studies on breastfeeding and MS published between database inception and May 18, 2022. Observational studies comparing persons with MS (pwMS) to healthy controls with regard to having been breastfed during the first two years of life were eligible for inclusion. A random effects meta-analysis was calculated to estimate pooled effect sizes using the Mantel-Haenszel method for dichotomous outcomes. The Newcastle-Ottawa Scale (NOS) was used for quality analysis.


RESULTS
15 studies (13 case-control, 2 cohort) were included of which 12 were rated as high quality. The meta-analysis of crude odds ratios (OR) yielded a risk estimate of ORcrude = 0.82 (95% CI 0.70-0.96) for MS in breastfed vs. non-breastfed individuals with substantial heterogeneity (I² = 68.2%). Using adjusted OR, when available, reduced heterogeneity (I² = 48.9%) and resulted in an ORadjusted = 0.86 (95% CI 0.75-0.99). Restricting the analysis to studies with high quality scores (i.e. ≥6/9 points) resulted in a combined ORcrude of 0.79 (95% CI 0.66-0.94) and an ORadjusted = 0.83 (95% CI 0.71-0.98), respectively.


DISCUSSION/CONCLUSION
The meta-analysis showed a small protective effect of having been breastfed on MS risk. This adds to the knowledge that breastfeeding is beneficial for the immunological health of a child. Future studies on the influence of having been breastfed on MS risk should apply a uniform definition of breastfeeding and investigate possible sex-specific aspects.