Background: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. A clear maternal effect has been shown in several population-based studies. This parent-of-origin effect could result from factors operating during gestation. It has been shown that a low birth weight increases the risk of several adult-onset diseases. In a population-based Canadian cohort, we investigated whether there is any difference in birth weight for MS index cases compared to spousal controls. Methods: Using the longitudinal Canadian database, we identified 6,188 MS index cases and 1,640 spousal controls with birth weight information. Additionally, data were available on 164 discordant MS twins. The birth weight was compared between index cases and controls as well as for twin pairs. Results: When stratifying by sex, no significant difference in birth weight was found (average female index case birth weight = 7.23 pounds, average female control birth weight = 7.19 pounds, p = 0.48; average male index case birth weight = 7.56 pounds, average male control birth weight = 7.55 pounds, p = 0.92). Furthermore, there was no difference in birth weight between affected and unaffected twins (average affected twin weight = 5.46 pounds, average unaffected twin weight = 5.44 pounds, p =0.85). Conclusions: The maternal effect in MS aetiology does not appear to act through a route that has an influence on birth weight. As birth weight is a relatively poor marker of fetal development, other factors involved in fetal and early development need to be explored to elucidate the mechanism of the increased MS risk conferred maternally.

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