In vivo assessment of the teratogenic potential of drugs in humans.

The difficulties in assessing the teratogenic potential of drugs used during pregnancy have been made evident by experiences with thalidomide and diethylstilbestrol (DES). In the case of thalidomide, the drug's ability to cause phocomelia tended to be species specific, and thus animal studies were unreliable indicators of teratogenicity in humans. With DES, the delayed appearance of injury, almost a generation after birth, indicates that short-term studies may fail to reveal serious effects. In both cases only the otherwise rare occurrence of the condition led to the suspicion of a cause-and-effect relationship. Although wide-spread use of drugs such as LSD, heroin, and marijuana has necessitated assessment of their teratogenic potential, a controlled investigation of their effects has so far been impossible to conduct. Both tobacco and alcohol have been associated with adverse effects on the fetus and neonate, but the precise mechanisms by which these effects occur are as yet unclear. There is also reason for concern about the teratogenic potential of environmental pollutants such as organic mercury compounds, lead, and radiation. Furthermore, the fetus may potentially be harmed if a particular drug is not administered (eg, insulin for diabetes during pregnancy). In the final analysis, any potential benefits of therapy for the mother must be weighed against known and unknown risks to the infant. Rational management requires an understanding of the physiologic and pharmacologic principles involved in each case and careful and judicious selection of drug therapy.