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Space-time analysis of Down syndrome: Results consistent with transient pre-disposing contagious agent

Lookup NU author(s): Dr Richard McNallyORCiD, Professor Judith RankinORCiD, Dr Mark ShirleyORCiD, Professor Stephen Rushton, Professor Tanja Pless-Mulloli

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Abstract

Background: Whilst maternal age is an established risk factor for Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), the aetiology and contribution of genetic and environmental factors remains unclear. We analysed for space-time clustering using high quality fully population-based data from a geographically defined region. Methods: The study included all cases of Patau, Edwards and Down syndrome, delivered during 1985-2003 and resident in the former Northern Region of England, including terminations of pregnancy for fetal anomaly. We applied the K-function test for space-time clustering with fixed thresholds of close in space and time using residential addresses at time of delivery. The Knox test was used to indicate the range over which the clustering effect occurred. Tests were repeated using nearest neighbour (NN) thresholds to adjust for variable population density. Results: The study analysed 116 cases of Patau syndrome, 240 cases of Edwards syndrome and 1084 cases of Down syndrome. There was evidence of space-time clustering for Down syndrome (fixed threshold of close in space: P = 0.01, NN threshold: P = 0.02), but little or no clustering for Patau (P = 0.57, P = 0.19) or Edwards (P = 0.37, P = 0.06) syndromes. Clustering of Down syndrome was associated with cases from more densely populated areas and evidence of clustering persisted when cases were restricted to maternal age <40 years. Conclusions: The highly novel space-time clustering for Down syndrome suggests an aetiological role for transient environmental factors, such as infections. © The Author 2008; all rights reserved.


Publication metadata

Author(s): McNally RJQ, Rankin J, Shirley MDF, Rushton SP, Pless-Mulloli T

Publication type: Article

Publication status: Published

Journal: International Journal of Epidemiology

Year: 2008

Volume: 37

Issue: 5

Pages: 1169-1179

ISSN (print): 0300-5771

ISSN (electronic): 1464-3685

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/ije/dyn083

DOI: 10.1093/ije/dyn083


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Funding

Funder referenceFunder name
Link Clinicians in the Northern Region
04/MRE04/25UK Health and Social Care Act (2001)

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