No effect of preterm birth on the risk of multiple sclerosis: a population based study

Sreeram V Ramagopalan,David A Dyment,Irene M Yee,William Valdar,A Dessa Sadovnick,Gabriele C Deluca,George C Ebers,Maria Criscuoli,Sarah-Michelle Orton,For The Canadian Collaborative Study Group

doi:10.1186/1471-2377-8-30

Abstract

BackgroundGenetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. A clear parent of origin effect has been shown in several populations, perhaps resulting from factors operating during gestation. Preterm birth (birth at less than 37 weeks gestational age) has been shown to result in long-term health problems, including impaired neurological development. Here, in a population-based cohort, we investigate whether preterm birth increases the risk to subsequently develop MS.MethodsWe identified 6585 MS index cases and 2509 spousal controls with preterm birth information from the Canadian Collaborative Project on Genetic Susceptibility to MS. Rates of individuals born preterm were compared for index cases and controls.ResultsThere were no significant differences between cases and controls with respect to preterm births. 370 (5.6%) MS index cases and 130 (5.2%) spousal controls were born preterm, p = 0.41.ConclusionPreterm birth does not appear to contribute to MS aetiology. Other factors involved in foetal and early development need to be explored to elucidate the mechanism of the increased risk conferred by the apparent maternal effect.

Highlights

Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility
Complete information from maternal informants on weeks gestation at birth as well as birth weight, duration of hospital stay, and the use of an incubator was available for 6585 index cases and 2509 spousal controls
No significant differences (p = 0.67 and p = 0.31 respectively) in the rates of preterm birth were observed when comparing female cases (280; 5.6%) and controls (46; 6.0%) – or male cases (90; 5.6%) and controls (84; 4.8%) (Table 2). This was confirmed by logistic regression analysis, which showed an effect of sex on the risk of MS (p < 1 × 10-16) but no effect of being born preterm (p = 0.65), or an interaction effect between sex and preterm birth (p = 0.31) on the likelihood of developing the disease

Summary

Introduction

Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. A clear parent of origin effect has been shown in several populations, perhaps resulting from factors operating during gestation. Preterm birth (birth at less than 37 weeks gestational age) has been shown to result in long-term health problems, including impaired neurological development. Like most common, complex traits, it is clear that genetic and environmental components play important roles, both independently and interactively [2]. A parent-of-origin effect (maternal) has been repeatedly observed in MS, based on data from studies of half-siblings [3], sibships including dizygotic twins [4], a large extended Dutch pedigree [5] and avuncular pairs [6] as well as a documented timing of birth effect [7]. 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

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Discussion

Conclusion