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Original Investigation |

Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom

Pedro María Rodríguez Cruz, MD, MSc1; Lucy Matthews, MRCP, DPhil1; Mike Boggild, FRACP2; Ana Cavey, CNS1; Cris S. Constantinescu, FRCP, PhD3; Nikos Evangelou, FRCP, DPhil3; Gavin Giovannoni, FRCP, PhD4; Orla Gray, MRCP5; Stanley Hawkins, FRCP6; Richard Nicholas, FRCP, PhD7; Maylin Oppenheimer, BMBCh1; Neil Robertson, FRCP, DM8; John Zajicek, FRCP, PhD9; Peter M. Rothwell, FRCP, FMedSci1; Jacqueline Palace, FRCP, DM1
[+] Author Affiliations
1Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England
2The Townsville Hospital, Queensland, Australia
3University of Nottingham, Nottingham, England
4Barts and The London School of Medicine and Dentistry, London, England
5South Eastern Health and Social Care Trust, Belfast, Northern Ireland
6Belfast Trust, Belfast, Northern Ireland
7Imperial College London, London, England
8Cardiff University, Cardiff, Wales
9University of St Andrews, St Andrews, Scotland
JAMA Neurol. 2016;73(8):954-960. doi:10.1001/jamaneurol.2016.1463.
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Importance  The reports of seasonal variation in the births of people who later develop multiple sclerosis (MS) have been challenged and attributed to the background pattern in the general population, resulting in a false association.

Objective  To study the seasonality of MS births after adjusting for temporal and regional confounding factors.

Design, Setting, and Participants  A study was conducted using case-control data from 8 MS-specialized centers from the United Kingdom, MS cases from a population-based study in the Lothian and Border regions of Scotland, and death records from the UK Registrar General. Participants included 21 138 patients with MS and control data from the UK Office of National Statistics and the UK government office regions. The seasonality of MS births was evaluated using the Walter and Elwood test, after adjusting for temporal and regional variations in the live births of the UK population. The study was conducted from January 16, 2014, to September 2, 2015.

Main Outcomes and Measures  Diagnosis of multiple sclerosis.

Results  Analysis of the general population indicated that seasonal differences are present across time and region in the United Kingdom, with both factors contributing to the monthly distribution of live births. We were able to demonstrate that, when adjusting for the temporal and regional variations in the live births of the UK population, there was a significant season of birth effect in patients with MS, with an increased risk of disease in the peak month (April) compared with the trough month (November) (odds ratio, 1.24; 95% CI, 1.10-1.41) and 15.68% fewer people who developed MS being born in November (observed to expected birth ratio, 0.840; 95% CI, 0.76-0.92).

Conclusions and Relevance  Season of birth is a risk factor for MS in the United Kingdom and cannot be attributed to the background pattern in the general population. The reasons for the variations in birth rates in the general population are unclear, but not taking them into consideration could lead to false-positive associations.

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Figure 1.
Seasonal Differences in the UK Government Office Regions (GORs) (1965-1999)

A, Deviance in the mean normalized monthly birth rates for the different GORs (data set C3 used). B, Seasonal differences between Scotland and the rest of the United Kingdom (Walter and Elwood test) (data set C3 used). Data sets are reported in the Table.

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Figure 2.
Residual Differences in Multiple Sclerosis (MS) Births per Month

A, Observed to expected MS birth ratios in the UK MS cohort (1938-1980) (data sets MS1-5 and C1-C2 used). B, Observed to expected MS birth ratios in the regional UK MS cohort (1965-1980) (data sets MS1-5 and C3 used). Data sets are reported in the Table. Error bars indicate 95% CI.

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Replicate this study in the Southern Hemisphere
Posted on August 10, 2016
Charles A. Pilcher MD FACEP
Physician, EvergreenHealth, Kirkland, WA, USA
Conflict of Interest: None Declared
The obvious next step is to replicate this study in the Southern Hemisphere.
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