title: Space-time analysis of Down syndrome: results consistent with transient pre-disposing contagious agent.
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.
authors.affiliation: School of Clinical Medical Sciences (Child Health), Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Richard J Q
authors.initials: RJ
authors.lastname: McNally
authors.forename: Judith
authors.initials: J
authors.lastname: Rankin
authors.forename: Mark D F
authors.initials: MD
authors.lastname: Shirley
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Rushton
authors.forename: Tanja
authors.initials: T
authors.lastname: Pless-Mulloli
mesh_terms: D004198:Disease Susceptibility; D018562:Disease Transmission, Infectious; D004314:Down Syndrome / Q000453:epidemiology* / Q000209:etiology; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008423:Maternal Age; D011156:Population Density; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D013029:Space-Time Clustering; D013997:Time Factors; D014314:Trisomy