Title: Seasonal Fluctuation of Multiple Sclerosis Births in Sardinia

Study results from different geographical areas provide some circumstantial evidences that, when compared to general population, people who later in life develop multiple sclerosis (MS) have a pattern of birth excess in spring and late summer, which may disclose an association with MS-predisposing environmental agents. To identify the presence of season-related cluster of MS birth in Sardinia we have designed a case-control study in the province of Sassari, Northern Sardinia, insular Italy, an area at very-high and increasing risk for MS. Mean birth incidence rate of people with MS (810 cases) on a three-and six-months basis were compared to that of two control populations: the MS unaffected siblings (1069), sharing genetic material with patients, and a representative number of births (247,612) of the general population of the study area. We found that the birth in months peaking in spring significantly represents one risk factor for future MS development. This seasonal deviation of MS births reveals an intriguing epidemiological overlap with common environmental agents, which may open a new scenario of hypothetical explanations for environmental factors perhaps affecting the CNS at the crucial time of myelination or shaping the newborn immune system.