As is typically the case in epidemiology and medicine, no "smoking gun" (single definitive piece of evidence that virus defects) should been cause of congenital have anticipated. Instead, the determination of a causal relationship would be expected to emerge from various lines of evidence, each of which suggests, but not on its own prove, that virus can cause adverse outcomes. Two approaches have been used to identify potential teratogens(exposures to mother during pregnancy that have a harmful effect on her embryo or fetus) first, the identification of a combination of a rare exposure and a rare defect(sometimes referred to as the astute clinician approach), o and second, the use of epidemiologic data to confirm an association Many teratogens were first identified by means of the rare exposure-rare defect approach, in cluding rubella virus, which was identified after an ophthalmologist noted a characteristic form of cataracts in infants whose mothers had ru bella during pregnancy," and heavy alcohol use, which was identified as a teratogen after the recognition of a characteristic pattern of malformations that became known as the fetal alcohol syndrome.? In contrast, some teratogens have been identified on the basis of epidemiologic studies(e.g., valproic acid was identified as teratogen after a case-control study showed an odds ratio of 20 for the association of spina bi fida with use of this drug during the first tri mester of pregnancy)