Teratogen update: Angiotensin‐converting enzyme inhibitors

Abstract

Occasionally there is a drug whose record in pregnancy is so frequently associated with adverse outcome of so specific a pattern that it becomes clear that its use must be restricted before scientific proof from epidemiological studies is obtained. I believe this to be the case with the drug class of ACEIs. There are mammalian models suggesting substantial fetotoxicity in a dose-related fashion. There is a strong and consistent pattern to the reported cases of ACEI-related adverse outcomes: the syndrome of oligohydramnios-anuria, neonatal hypotension, renal dysplasia, and hypocalvaria is too specific in association with the use of these drugs to be ignored. There is a very plausible biologic mechanism to explain the relationship. The features of ACEI fetopathy suggest that the underlying pathogenetic mechanism is fetal hypotension, which may also result from other exposures. Thus, while the fetopathy may not be truly specific to ACEIs, they are particularly liable to produce adverse fetal renal effects with their sequels (anuria-oligohydramnios, pulmonary hypoplasia, growth restriction) and hypocalvaria.