Principles of teratogenicity

Abstract

An agent is now considered a teratogen if its administration to the pregnant mother causes, directly or indirectly, structural or functional abnormalities in the fetus, or in the child after birth, which may not be apparent until later life. A teratogen can induce chromosomal abnormalities, prevent implantation of the conceptus, and cause abortion of the early embryo, late fetal death, congenital malformations, or intrauterine growth retardation. In the neonate there may be functional impairment, e.g. deafness. Behavioural abnormalities and mental retardation may also occur. Little is known about specific teratogenic mechanisms but some general principles have been formulated. Susceptibility to teratogens is genetically determined. Teratogenic agents may be beneficial or harmless to the mother but harmful or lethal to the embryo or the fetus. Most drugs and chemicals will cross the placenta. The timing of the exposure is critically important and determines the type of fetal toxicity that might occur, e.g. malformation or functional impairment. Teratogenicity is usually dose-dependent, and there is evidence that the teratogenicity of a drug may be enhanced by co-administration of a second drug.