The use of dysmorphology in birth defects epidemiology

Most human teratogens have been identified by the clinical recognition of characteristic patterns of congenital anomalies among children whose mothers were exposed to a particular agent during pregnancy. Although this dysmorphologic method has been valuable, it is criticized because it is not easily amenable to statistical evaluation. Conventional birth defects epidemiological studies are designed to permit rigorous statistical assessment, but such investigations usually classify congenital anomalies without adequate consideration of their known etiological heterogeneity. It is possible to combine the best aspects of these two approaches to identifying human teratogens in a "dysmorphologic case/control study." Instead of including all available cases with a given defect, only individuals having the anomaly in the context of a multiple congenital anomaly pattern without a recognizable cause would be selected for inclusion among the case group. The frequency of exposure to the putative teratogen would be determined among these selected cases and among appropriately chosen controls; conventional statistical analysis would then be performed. Although this design reduces the size of the case group compared to a conventional case/control study, the statistical power is unchanged or increased. In addition, biological plausibility is increased by concentrating upon a group of cases that is more likely to have a teratogenic cause.