Postmarketing surveillance for human teratogenicity: A model approach

Background: Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a s ingle major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this r eport is to outline a complementary approach that can be used in addition t o other more established methods to provide the most comprehensive evaluati on of prenatal exposures with respect to teratogenicity. Methods: We describe a multicenter prospective cohort study design involvin g dysmorphological assessment of liveborn infants. This design uses the Org anization of Teratology Information Services, a North American network of i nformation providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. Results: The focused cohort study design allows for evaluation of a spectru m of adverse pregnancy outcomes ranging from spontaneous abortion to functi onal deficit. While sample sizes are typically inadequate to identify incre ased risks for single major malformations, the use of dysmorphological exam inations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. Conclusions: As the known human teratogens are generally associated with pa tterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an accept able level of confidence regarding the risk or safety of specific exposures during pregnancy. (C) 2001 Wiley-Liss, Inc.