Exposure to tobacco smoke during pregnancy and the risk of multiple sclerosis in offspring: A systematic review and meta-analysis.

INTRODUCTION

Smoking is a common factor that contributes to the development of Multiple sclerosis during embryogenesis. Several studies found a correlation between maternal or paternal smoking and the development of Multiple sclerosis in offspring. Given inconclusive findings from recent studies, we aim to conduct a systematic review and meta-analysis of the relation between parental tobacco smoking and the risk of Multiple sclerosis in offspring.

METHODS

We systematically conducted comprehensive search screening including (PubMed, Scopus, Web of Science, Embase, and Cochrane Library) until July 2025. This study aimed to assess the relation between exposure to tobacco smoke during pregnancy (maternal and paternal smoking) and the risk of Multiple sclerosis in offspring. Pooled estimates were calculated using a random-effects model. The PROSPERO registration is CRD420251117243.

RESULTS

This study included nine studies involving 1,405,641 participants, including 5,452 Multiple sclerosis patients. We did not find a correlation between maternal smoking during and before pregnancy and risk of Multiple sclerosis in offspring (OR = 1.13, 95% CI [0.9, 1.43], P-value= 0.30, I2= 53.7%), (OR = 1.11, 95% CI [0.83, 1.48], P-value= 0.48, I2 = 0%) respectively. We found a statistically significant association between paternal smoking and the risk of Multiple sclerosis in offspring (OR 1.62, 95% CI [1.24; 2.11], P-value= 0.00036, I2= 0%).

CONCLUSION

These findings highlight a complex relationship between parental smoking and offspring risk of MS. We observed no clear association for maternal smoking, whereas paternal smoking was associated with an increased risk in offspring. However, neither result is definitive, and further well-designed prospective studies are required to confirm these associations and clarify underlying mechanisms.