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Month of birth, vitamin D and risk of immune-mediated disease: a case control study

Giulio Disanto12, George Chaplin3, Julia M Morahan12, Gavin Giovannoni4, Elina Hyppönen5, George C Ebers12* and Sreeram V Ramagopalan1246*

Author Affiliations

1 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK OX3 7BN

2 Department of Clinical Neurology, University of Oxford, Oxford, UK OX3 9DU

3 Department of Anthropology, The Pennsylvania State University, Pennsylvania, United States of America, 16802

4 Blizard Institute of Cell and Molecular Science, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK, E1 2AT

5 Centre for Paediatric Epidemiology and Biostatistics and MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, UK, WC1N 1EH

6 London School of Hygiene and Tropical Medicine, London, UK, WC1E 7HT

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BMC Medicine 2012, 10:69  doi:10.1186/1741-7015-10-69

Published: 6 July 2012



A season of birth effect in immune-mediated diseases (ID) such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB) light exposure and vitamin D status during gestation.


The monthly distribution of births of patients with ID from the UK (n = 115,172) was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient.


The distributions of ID births significantly differed from that of the general population (P = 5e-12) with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P < 0.0001) and a trough in October (odds ratio = 0.945, 95% confidence interval = 0.925, 0.966, P < 0.0001). Stratification by disease subtype showed seasonality in all ID but Crohn's disease. The risk of ID was inversely correlated with predicted second trimester UVB exposure (Spearman's rho = -0.49, P = 0.00005) and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003).


The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.