Pharmacogenetics of drug-induced birth defects: what is known so far?

Abstract

A literature review was performed to collect information on the role of pharmacogenetics in six proposed teratogenic mechanisms associated with drug use during pregnancy: folate antagonism, oxidative stress, angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism, cyclooxygenase-1 and -2 inhibition, 5-hydroxytryptamine-reuptake inhibition and drug transporters in the placenta. Data on the direct relationship between pharmacogenetics and drug-induced birth defects were found for folate metabolism, oxidative stress caused by phenytoin exposure and drug transporters in the placenta. Although no specific data to support pharmacogenetic-related birth defects were found for the NSAIDs, paroxetine and fluoxetine, it might be expected that polymorphisms modify their teratogenic effects. The usually low prevalence of drug-induced malformations impedes the demonstration of the contribution of pharmacogenetics. Large-scale studies, preferably case–control studies, are needed.