Objective: The National Down Syndrome Project (NDSP), based at Emory University in Atlanta, Georgia, represents a multi-site, population-based, case-control study with two major aims: (1) to identify molecular and epidemiological factors contributing to chromosome nondisjunction and the consequent packaging of an extra chromosome into an egg or sperm, and (2) to identify risk factors for Down syndrome-associated birth defects.
Methods: The six national sites represent approximately 11% of U.S. births. Cases were newborns with Down syndrome (trisomy 21), and controls were infants without major birth defects randomly selected from the same birth populations. Biological samples were collected from case infants and their parents, and genetic markers were typed to determine the parental origin of chromosome 21 nondisjunction. Each site interviewed parents of case and control infants addressing pregnancy, medical and family history, occupation, and exposures. Sites collected medical information on case infants.
Results: The NDSP enrolled 907 infants as cases and 977 infants as controls (participation rates: 60.7% for cases; 56.9% for controls). Participation rates varied widely by site as did important demographic factors such as maternal age, race, and education. Nondisjunction during oogenesis accounted for 93.2% of the cases. Errors in spermatogenesis were found in 4.1%, and 2.7% were post-zygotic errors.
Conclusions: This exceptional compilation of questionnaire, clinical, and molecular data makes the NDSP a unique resource for ongoing studies of the etiology and phenotypic consequences of trisomy 21. The combined approach increases study power by defining subgroups of cases by the origin of nondisjunction. This report describes the design and successful implementation of the