Teratogen

Teratology is the study of the effects of exposures during pregnancy on a developing fetus. These exposures, known as teratogens, can be quite varied and include agents such as medications, illicit drugs, infectious diseases, maternal metabolic states, and occupational and environmental exposures. A teratogen can cause a spontaneous loss of pregnancy or structural and/or functional disability in a child. It has been estimated that 5% to 10% of birth defects are due to an exposure during pregnancy.

The following are the five characteristics of a teratogen. The first characteristic is that the occurrence of the birth defect or pattern of birth defects is higher in the population exposed to the teratogen as compared with the general population. Since 3% to 5% of all newborns have a birth defect, the number of malformed infants must exceed that of the background risk. More specifically, the occurrence of the exact malformation or pattern of malformations must be increased. The second characteristic is that an animal model should duplicate the effect seen in humans. Animal models serve as a good system for ‘red flagging’ an agent but can never be used to directly determine effects from human exposure or the magnitude of any potential risk. The third characteristic is that a dose-response relationship has been established; the greater the exposure, the more severe the phenotypic effect. A corresponding concept is that of a threshold effect; effects are only seen above a specific exposure level. The fourth characteristic is that there should be a plausible biologic explanation for the mechanism of action. The fifth characteristic asserts that a genetic susceptibility increases the chance of an adverse outcome from the exposure. This area of pharmacogenetics holds great promise for advancing our understanding of human teratology and the provision of individualized risk assessments.

Using the above principles, it is possible to develop a risk assessment for an individual exposed pregnancy. Several pieces of information, including the timing of the exposure, the dose of the agent, and family medical and pregnancy history information, are critical. A review of the available literature is essential. Scientific data concerning outcomes of exposed pregnancies are often conflicting, difficult to locate, and hard to interpret. Much of the data are in the form of case reports, animal studies, and retrospective reviews. To provide complete information, it may be necessary to consult various resources. It is important to appreciate the riskbenefit ratio regarding a particular agent to provide an individualized risk assessment on which pregnancy management may be based.

Despite scientific advances in clinical teratology, exposures prior to and during pregnancy still cause great anxiety and misunderstanding among both the public and health care professionals. Teratology Information Services (TIS) are comprehensive, multidisciplinary resources that provide information on prenatal exposures to health care providers and the public. The national consortium of individuals providing these services is the Organization of Teratology Information Specialists. An individual TIS has three components: service (toll-free, confidential phone consultations), education (to health care providers and the public), and research (national and international studies on specific agents).

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