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BMC Med. 2012; 10: 69.
Published online Jul 6, 2012. doi:  10.1186/1741-7015-10-69
PMCID: PMC3395583
Month of birth, vitamin D and risk of immune-mediated disease: a case control study
Giulio Disanto,#1,2 George Chaplin,#3 Julia M Morahan,1,2 Gavin Giovannoni,4 Elina Hyppönen,5 George C Ebers,corresponding author1,2 and Sreeram V Ramagopalancorresponding author1,2,4,6
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK OX3 7BN
2Department of Clinical Neurology, University of Oxford, Oxford, UK OX3 9DU
3Department of Anthropology, The Pennsylvania State University, Pennsylvania, United States of America, 16802
4Blizard Institute of Cell and Molecular Science, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK, E1 2AT
5Centre for Paediatric Epidemiology and Biostatistics and MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, UK, WC1N 1EH
6London School of Hygiene and Tropical Medicine, London, UK, WC1E 7HT
corresponding authorCorresponding author.
#Contributed equally.
Giulio Disanto: giulio.disanto/at/well.ox.ac.uk; George Chaplin: guc5/at/psu.edu; Julia M Morahan: julia.morahan/at/well.ox.ac.uk; Gavin Giovannoni: g.giovannoni/at/qmul.ac.uk; Elina Hyppönen: e.hypponen/at/ich.ucl.ac.uk; George C Ebers: george.ebers/at/clneuro.ox.ac.uk; Sreeram V Ramagopalan: s.ramagopalan/at/qmul.ac.uk
Received April 24, 2012; Accepted July 6, 2012.
Abstract
Background
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.
Methods
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.
Results
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).
Conclusions
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.
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