Panel discussion: Drugs and fetal metabolism

DR. SUMNER YAFFE: It seems to me that the morning and afternoon sessions complemented each other. This morning we heard epidemiologic evidence that many women take drugs during pregnancy. We also heard that these drugs may harm infants who are unwanted recipients although, except for a few drugs, we don't have much clear‐cut evidence about this. We also heard Dr. Hellman in his keynote address paint out the concern about producing a baby with the maximum opportunity to have his genes expressed. We should also consider that therapeutic benefits may occur under certain circumstances when drugs are administered orally, or by amniotic fluid injection, to pregnant women. Indeed, we have entered the era of fetal therapeutics in which drugs will be administered either directly or indirectly for the specific benefit of the fetus. In present clinical practice, the dose of a drug given to a pregnant woman is usually the same as that given to a non‐pregnant woman. It is not known whether those doses are appropriate, because it is not known whether drug metabolism and disposition differ in pregnant and non‐pregnant women. This is an area that needs considerable investigation. Another implication of this morning's meeting is that the term teratogenesis needs to be redefined. The new definition should include not only anatomic malformations, but also late behavioral and biochemical effects that are much more difficult to detect. This kind of consideration makes it very difficult to evaluate the safety of drug administration during pregnancy. Predictive tests that can be used in the evaluation of drug safety in pregnant women are needed very badly. I believe that Dr. Nebert's presentation indicated the utility of tissue culture studies with fetal cells for predicting the cellular toxicity of drugs. Dr. Nebert also pointed out the importance of looking at the metabolic capabilities of each particular host and he indicated the importance of the genetic makeup of each individual for drug toxicity.