Pharmacogenetic Screening for Susceptibility to Fetal Malformations in Women

OBJECTIVE:To present a review of the literature and research on the pharmacogenetics of congenital defects, with a focus on the need for predictive maternal genotype assays.DATA SOURCE:MEDLINE searches (January 1985–January 1999), past reference reviews, and unpublished research.STUDY SELECTION:Review of relevant human, animal, and basic science studies.DATA EXTRACTION:Data on research on polymorphisms, genotyping, cytochrome P450 enzyme systems, epoxide hydrolase, folate metabolism, metabolism of anticonvulsant medications, molecular genetics of neural tube defects, variations in drug metabolism, and environmental exposures were evaluated.DATA SYNTHESIS:Data synthesis includes not only a review of the literature but suggests ways such data might be used to facilitate the development of maternal genotype assays, with the goal of preventing birth defects.CONCLUSIONS:Individuals vary in how they metabolize drugs and handle toxic environmental exposures. In an ideal pregnancy, there is no or limited exposure...