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 a teratogen after a case–control study showed an odds ratio of 20 for the association of spina bifida with use of this drug during the first trimester of pregnancy).