Birth defects are common—2 to 3 percent of all newborns have a major congenital abnormality detectable at birth (Cragan, 2009; Dolk, 2010). By age 5, another 3 percent have been diagnosed with a malformation, and by age 18, another 8 to 10 percent have one or more apparent functional or developmental abnormalities. Importantly, nearly 70 percent of birth defects do not have an obvious etiology, and of those with an identified cause, it is far more likely to be genetic than teratogenic (Schardein, 2000; Wlodarczyk, 2011). The Food and Drug Administration (FDA) (2005b) estimates that less than 1 percent of all birth defects are caused by medications. Examples of medications considered teratogenic are shown in Table 12-1.
TABLE 12-1Selected Teratogens and Fetotoxic Agents
Although only a relatively small number of medications have proven harmful effects, there is significant concern surrounding medication use in pregnancy. This is because most pregnant women take medications and for most medications, available safety data are limited. In a review of more than 150,000 pregnancies, 40 percent of women were prescribed a medication other than multivitamins in the first trimester (Andrade, 2004). More recently, data from the National Birth Defects Prevention Study showed that women use an average of 2 to 3 medications per pregnancy and that 70 percent take medication in the first trimester (Mitchell, 2011).
Despite improvements in safety information, data are particularly limited for newer medications. For example, in a review of medications approved by the FDA between 2000 and 2010, the Teratogen Information System (TERIS) expert advisory board deemed the pregnancy risk “undetermined” for more than 95 percent (Adam, 2011).
The study of birth defects and their etiology is termed teratology. The word teratogen is derived from the Greek teratos, meaning monster. Pragmatically, a teratogen may be defined as any agent that acts during embryonic or fetal development to produce a permanent alteration of form or function. Thus, a teratogen may be a drug or other chemical substance, a physical or environmental factor such as heat or radiation, a maternal metabolite such as in phenylketonuria or diabetes, a genetic abnormality, or an infection. Tightly defined, a teratogen causes structural abnormalities, whereas a hadegen—after the god Hades—is an agent that interferes with normal maturation and function of an organ. A trophogen is an agent that alters growth. Substances in the latter two groups typically affect development in ...