Childhood and Adolescent Environmental Risk Factors for Multiple Sclerosis: A Systematic Review With Meta-Analysis

Background: We aimed to provide updated evidence from the current literature regarding pediatric environmental factors associated with the risk of developing multiple sclerosis (MS). Methods: Articles were searched in PubMed, SciVerse ScienceDirect, and Web of Science. We included all clinical studies assessing the occurrence of MS at any age in association with the exposure to any environmental risk factor during childhood or adolescence. The main outcome was the occurrence of MS. The quality assessment was performed with the critical appraisal checklist for case-control studies. Pooled unadjusted effect sizes (OR) were calculated and reported with a 95% CI from random-effects meta-analysis. Results: The review included 87 studies conducted across 20 countries. The studies analyzed diverse environmental risk factors, including infections, vaccinations, tobacco exposure, body mass index, and other pediatric exposures. EBV infection showed a significant positive association with MS risk (ES = 2.38, 95% CI = 1.80-3.15). Breastfeeding showed limited protective associations, and various adverse social experiences like bullying and sexual abuse were linked to increased MS risk. Active smoking during childhood/adolescence and obesity during these periods were associated with higher MS risk, while normal body mass index was protective. Antibiotic and chemical exposures, as well as vitamin D deficiency, were linked to higher MS risk. The review highlighted substantial heterogeneity and identified publication bias in studies on infections and vaccinations. Conclusions: Environmental risk factors for MS are important during childhood and adolescence. The first 20 years are a key window for prevention and should be seen as an opportunity.