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Background and purpose Many hypotheses on the etiopathogenesis of multiple sclerosis ( MS) focus on risk factors occurring early in life. This study examined the variability of birth cohort trends in international MS data by means of age-period-cohort ( APC) analysis. Methods The data from 25 countries were taken from the WHO mortality database. Data were encoded according to the International Classification of Diseases and covered slightly varying periods between 1951 and 2009. The APC analyses were based on logit models applied to cohort tables with 5-year age- and period intervals. Results In most countries, the birth cohort estimates peaked in those born in the first half of the 20th century. In countries from Central and Western Europe, the peak concerned those born before and around 1920. A second group of countries ( Denmark, Sweden, Italy, Ireland, Scotland) shared a later peak amongst cohorts born in the 1920s and 1930s. Group 3 included Commonwealth countries, the USA and Norway, with a double or extended peak starting in the 1910s or 1920s, and ending by the 1950s. The fourth group, consisting of Mediterranean countries and Finland, was characterized by a steady increase in the birth cohort estimates until the 1950s. The fifth group with countries from Eastern Europe and Japan showed no particular pattern. Conclusions Birth cohort trends have influenced the change in MS risk across the 20th century in many Western countries. This silent epidemic points to a most important but unknown latent risk factor in MS. [ABSTRACT FROM AUTHOR]