title: Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies.
abstract: BACKGROUND
  Classification and analysis of congenital heart defects (CHD) in etiologic studies is particularly challenging because of diversity of cardiac phenotypes and underlying developmental mechanisms. We describe an approach to classification for risk assessment of CHD based on developmental and epidemiologic considerations, and apply it to data from the National Birth Defect Prevention Study (NBDPS).
  
  
  METHODS
  The classification system incorporated the three dimensions of cardiac phenotype, cardiac complexity, and extracardiac anomalies. The system was designed to facilitate the assessment of simple isolated defects and common associations. A team with cardiologic expertise applied the system to a large sample from the NBDPS.
  
  
  RESULTS
  Of the 4,703 cases of CHDs in the NBDPS with birth years 1997 through 2002, 63.6% were simple, isolated cases. Specific associations of CHDs represented the majority of the remainder. The mapping strategy generated relatively large samples for most cardiac phenotypes and provided enough detail to isolate important subgroups of CHDs that may differ by etiology or mechanism.
  
  
  CONCLUSIONS
  Classification of CHDs that considers cardiac and extracardiac phenotypes is practically feasible, and yields manageable groups of well-characterized phenotypes. Although best suited for large studies, this approach to classification and analysis can be a flexible and powerful tool in many types of etiologic studies of heart defects.
authors.affiliation: Division of Medical Genetics, University of Utah, Salt Lake City, Utah 84132, USA. lorenzo.botto@hsc.edu
authors.forename: Lorenzo D
authors.initials: LD
authors.lastname: Botto
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
authors.forename: Tiffany
authors.initials: T
authors.lastname: Riehle-Colarusso
authors.forename: Sadia
authors.initials: S
authors.lastname: Malik
authors.forename: Adolfo
authors.initials: A
authors.lastname: Correa
mesh_terms: D006330:Heart Defects, Congenital / Q000145:classification* / Q000178:diet therapy / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D006801:Humans; D010641:Phenotype; D012189:Retrospective Studies; D018570:Risk Assessment; D014481:United States