Application of data screening to drug exposure in large risk factor studies of birth defects.
BACKGROUND
Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying those medications that most warrant attention by using a "screen" program that calculates odds ratios for pairs of exposures and specific birth defects.


METHODS
We discuss the development of this tool and illustrate its application to two large risk factor studies, the Slone Epidemiology Center's Birth Defects Study and the Centers for Disease Control and Prevention's National Birth Defects Prevention Study, ideal settings for the systematic study of risks and relative safety of drugs in relation to birth defects while recognizing the inherent limitations of such an approach.


RESULTS
Suggestions for establishing criteria for exposures and outcomes that balance the need for specific details with the practical considerations of sample size and volume of output are presented. Selection of appropriate exposure reference categories and control groups is also discussed, as well as the need to address potential confounding. An example that motivated a detailed investigation of possible associations between a medication (butalbital) and selected specific birth defects is provided.


CONCLUSION
While screening programs such as the one described can be a valuable tool for exploring potential associations in large data bases, they must be applied with caution. The issue of multiple testing and chance findings is a major concern. While statistics are a necessary component, human judgment must be an integral part of the process.
['Louik|Carol|C|', 'Werler|Martha|M|', 'Anderka|Marlene|M|', 'Mitchell|Allen A|AA|']
D000014:Abnormalities, Drug-Induced D016022:Case-Control Studies D002487:Centers for Disease Control and Prevention, U.S. D000013:Congenital Abnormalities D016208:Databases, Factual D005260:Female D006801:Humans D004364:Pharmaceutical Preparations D011159:Population Surveillance D011247:Pregnancy D012307:Risk Factors D014481:United States
data screening birth defects medication use statistics large databases