Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by myelin loss, varying degrees of axonal pathology and progressive neurological dysfunction . With a prevalence of about 1/1000, MS is the most common cause of acquired neurological disability in young adults of Northern European descent  other than trauma. The aetiology of MS remains elusive. However, like most common, complex traits, it is clear that genetic and environmental components play important roles, both independently and interactively .
A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on data from studies of half-siblings , sibships including dizygotic twins , a large extended Dutch pedigree  and avuncular pairs  as well as a documented timing of birth effect . The biological basis of this parent-of-origin effect is as yet unknown, but may arise from environmental components, gene-environment interactions and/or epigenetic modifications.
A "preterm" birth is defined as occurring at less than 37 weeks gestational age . Preterm birth has been increasing in frequency over the last few decades in Western societies, now accounting for some 7% of all births in Canada . Although the cause of preterm labour has no precise aetiology, several maternal risk factors have been implicated, including smoking, stress, infection and nutritional status . Additionally, preterm birth has been observed to vary seasonally . With improvements in perinatal care, such as surfactant therapy and ventilator strategies, survival has steadily improved . This however has been accompanied by concerns about a higher risk of long term health problems among survivors . Although most organs are immature, the brain and lungs are especially susceptible to the consequences of preterm birth, leading to high rates of neurological complications including cerebral palsy, cognitive deficits and neuro-sensory impairments . Preterm birth has been shown to alter brain structure with reduced total cerebral tissue volume and delayed myelination compared to term births .
In MS, plaque load does not correlate with axonal loss , the accumulation of axonal loss is associated with irreversible disability  and natural history data show that the progressive phase is an age-dependent degenerative process . Taken together, these data suggest that a possible mechanism affecting neurodegeneration/neurodevelopment may be involved in MS pathogenesis.
Here, in a population-based cohort, we investigate whether preterm birth increases the risk to subsequently develop MS. To the best of our knowledge, this is the first study on this specific topic.