Human Genetics

, Volume 125, Issue 1, pp 41–52

Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction: a report from the Atlanta and National Down Syndrome Projects


    • Department of Human GeneticsEmory University
  • Sallie B. Freeman
    • Department of Human GeneticsEmory University
  • Charlotte Druschel
    • New York State Department of Health 
  • Charlotte A. Hobbs
    • Department of Pediatrics, College of MedicineUniversity of Arkansas for Medical Sciences
  • Leslie A. O’Leary
    • Centers for Disease Control and PreventionNational Center on Birth Defects and Developmental Disabilities
  • Paul A. Romitti
    • Department of Epidemiology, College of Public HealthThe University of Iowa
  • Marjorie H. Royle
    • New Jersey Department of Health and Senior Services
  • Claudine P. Torfs
    • Birth Defects StudiesPublic Health Institute
  • Stephanie L. Sherman
    • Department of Human GeneticsEmory University
Original Investigation

DOI: 10.1007/s00439-008-0603-8

Cite this article as:
Allen, E.G., Freeman, S.B., Druschel, C. et al. Hum Genet (2009) 125: 41. doi:10.1007/s00439-008-0603-8


We examined the association between maternal age and chromosome 21 nondisjunction by origin of the meiotic error. We analyzed data from two population-based, case–control studies: Atlanta Down Syndrome Project (1989–1999) and National Down Syndrome Project (2001–2004). Cases were live born infants with trisomy 21 and controls were infants without trisomy 21 delivered in the same geographical regions. We enrolled 1,215 of 1,881 eligible case families and 1,375 of 2,293 controls. We report four primary findings. First, the significant association between advanced maternal age and chromosome 21 nondisjunction was restricted to meiotic errors in the egg; the association was not observed in sperm or in post-zygotic mitotic errors. Second, advanced maternal age was significantly associated with both meiosis I (MI) and meiosis II (MII). For example, compared to mothers of controls, mothers of infants with trisomy 21 due to MI nondisjunction were 8.5 times more likely to be ≥40 years old than 20–24 years old at the birth of the index case (95% CI = 5.6–12.9). Where nondisjunction occurred in MII, mothers were 15.1 times more likely to be ≥40 years (95% CI = 8.4–27.3). Third, the ratio of MI to MII errors differed by maternal age. The ratio was lower among women <19 years of age and those ≥40 years (2.1, 2.3, respectively) and higher in the middle age group (3.6). Lastly, we found no effect of grand-maternal age on the risk for maternal nondisjunction. This study emphasizes the complex association between advanced maternal age and nondisjunction of chromosome 21 during oogenesis.

Copyright information

© Springer-Verlag 2008