Drug Therapy in Pregnancy

Major birth defects affect 3 to 5% of all live births. Most are of unknown etiology, but 1 to 3% of these are thought to be due to pharmaceutical or environmental agents. A teratogen is any chemical, pharmacologic, environmental, or mechanical agent that can cause deviant or disruptive development of the conceptus. Included in this definition are functional impairment, growth restriction, and congenital malformations. These may range from subtle neurobehavioral effects to devastating physiologic effects and physical deformities, including fetal death. Why one pregnancy would be affected and not another remains to be elucidated. Highly teratogenic medications seem to be few in number, estimated at well below 50 agents (Box 180-1). The process of establishing teratogenicity is tedious and often flawed. Animal research, although valuable in determining risk initially, is not always applicable to humans, and controlled prospective human studies are generally not performed for ethical reasons. As a result, much of our current knowledge on teratogenicity has been derived from case reports, case-control studies, or cohort studies, which are inherently weak in establishing a causal relationship. These reports are often complicated by a multitude of confounding factors, making the determination of a causal link between a specific exposure and malformations difficult. The genetic background of the fetus, timing and duration of the exposure, environmental factors, multiple exposures, nutritional deficits, maternal illness, and illicit drug use all contribute to the outcome of pregnancy. Large population studies are needed to understand the connection between the outcome of a pregnancy and an associated in utero exposure. Finally, as in the case of diethylstilbestrol, teratogenicity may not be apparent for years after birth.