Background: Prenatal and perinatal factors are believed to contribute to the risk of developing multiple sclerosis (MS).

Objective: This study was designed to evaluate whether mode of delivery (vaginal versus cesarean section), as a perinatal factor, affects susceptibility to MS.

Methods: MS patients were recruited from the MS registry of Isfahan Multiple Sclerosis Society (IMSS) and were compared with their healthy siblings. Data regarding mode of delivery, birth order, and gestation week of birth were obtained through a specially designed questionnaire. Preterm or post term deliveries were excluded. We used conditional logistic regression statistics and adjusted for gender and birth order.

Results: This study included 1349 participants (449 MS patients and 900 controls). Subjects who were born by cesarean section had significant risk of MS (odds ratio, OR = 2.51; 95% confidence interval, CI: 1.43–4.41; p = 0.001). There was significant MS risk for females who were born by cesarean section (OR = 2.69, 95% CI: 1.30–5.58; p = 0.008), but not for males (OR = 2.25, 95% CI: 0.90–5.63; p = 0.082). The mean age at onset was lower in MS patients born by cesarean section (24.58 ± 6.33) compared with that of patients born by vaginal delivery (27.59 ± 7.97; p = 0.041). There was no significant difference between the two groups for birth order (p = 0.417).

Conclusion: Our results suggest that those born by vaginal delivery are at a lower risk of subsequent MS. These preliminary findings will need to be addressed in a much larger and preferably prospective study.