Guidelines for case classification for the National Birth Defects Prevention Study

Birth Defects Res A Clin Mol Teratol. 2003 Mar;67(3):193-201. doi: 10.1002/bdra.10012.


Background: Previous studies have suggested that etiologic heterogeneity may complicate epidemiologic analyses designed to identify risk factors for birth defects. Case classification uses knowledge of embryologic and pathogenetic mechanisms to make case groups more homogeneous and is important to the success of birth defects studies.

Methods: The goal of the National Birth Defects Prevention Study (NBDPS), an ongoing multi-site case-control study, is to identify environmental and genetic risk factors for birth defects. Information on environmental risk factors is collected through an hour-long maternal interview, and DNA is collected from the infant and both parents for evaluation of genetic risk factors. Clinical data on infants are reviewed by clinical geneticists to ensure they meet the detailed case definitions developed specifically for the study. To standardize the methods of case classification for the study, an algorithm has been developed to guide NBDPS clinical geneticists in this process.

Results: Methods for case classification into isolated, multiple, and syndrome categories are described. Defects considered minor for the purposes of case classification are defined. Differences in the approach to case classification for studies of specific defects and of specific exposures are noted.

Conclusions: The case classification schema developed for the NBDPS may be of value to other clinicians working on epidemiologic studies of birth defects etiology. Consideration of these guidelines will lead to more comparable case groups, an important element of careful studies aimed at identifying risk factors for birth defects.

Publication types

  • Guideline

MeSH terms

  • Adult
  • Algorithms
  • Congenital Abnormalities* / classification
  • Congenital Abnormalities* / etiology
  • Congenital Abnormalities* / prevention & control
  • DNA / analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Maternal Exposure
  • Population Surveillance / methods*
  • Pregnancy
  • Registries*
  • Risk Factors
  • United States / epidemiology


  • DNA