Reducing Early-Life Smoke Exposure as a Preventive Strategy for Pediatric Multiple Sclerosis: Results from the PEDIGREE Study

INTRODUCTION: Assessing the environmental impact on multiple sclerosis (MS) is complex because of long disease latency and potential recall bias, especially for perinatal exposures. This study aimed to investigate the association between parental smoking and the development of pediatric MS (PedMS). METHODS: As part of the Italian multicenter PEDIGREE study, the PEQ-IT questionnaire was used for prospective data collection. We enrolled subjects under 18 years with PedMS (2013 Krupp criteria) and disease duration ≤ 5 years from onset, along with matched controls. RESULTS: The study included 114 PedMS cases and 121 controls. Female participants represented 77.2% of cases and 54.4% of controls, with a mean (SD) age of 16.8 (2.7) and 13.5 (4.9) years, respectively. The mean (SD) age at MS onset was 14.2 (2.6) years, and the median EDSS score was 1.0 (range 0-4.0). PedMS risk was higher in subjects with fathers who were current smokers (crude OR 1.94, 95% CI 1.10-3.40) or who smoked 3 months' pre-pregnancy (crude OR 1.79, 95% CI 1.03-3.11). The risk increased when both parents smoked (crude OR 2.03, 95% CI 1.12-3.68) and was highest when both smoked 3 months before pregnancy (crude OR 10.79, 95% CI 1.30-89.54), even after adjustments. No significant association was found with maternal smoking. CONCLUSION: Parental smoking, particularly paternal smoking current habit and before pregnancy, may increase the risk of PedMS. Promoting smoke-free behaviors among parents could therefore represent a feasible preventive approach to limit early-life environmental factors involved in disease susceptibility.