IJE Advance Access published online on May 8, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn083
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Space-time analysis of Down syndrome: results consistent with transient pre-disposing contagious agent
1 School of Clinical Medical Sciences (Child Health), Newcastle University, Newcastle upon Tyne, UK.
2 Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
3 Regional Maternity Survey Office, Newcastle upon Tyne, UK.
4 Institute for Research on Environment and Sustainability, Newcastle University, Newcastle upon Tyne, UK.
* Corresponding author. Sir James Spence Institute, Newcastle University, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK. E-mail: Richard.McNally{at}ncl.ac.uk
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Abstract |
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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.
Keywords Congenital abnormality, Down syndrome, Edwards syndrome, Patau syndrome, aetiology, environment, space-time clustering
Accepted 7 April 2008
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  J. K Morris Commentary: Clustering in Down syndrome Int. J. Epidemiol., October 1, 2008; 37(5): 1179 - 1180. [Full Text] [PDF]
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