Fetal effects of maternally administered clonidine and angiotensin-converting enzyme inhibitors

Abstract

Clonidine is an alpha-adrenergic agonist. It crosses the placenta extensively. No teratogenic effect is known in animals or in clinical practice but the question of a possible long-term behavioral teratogenicity has recently been pointed out. Clonidine does not seem to be deleterious for fetal growth, mortality and morbidity. Nothing is known about the consequences on fetal hemodynamics. The angiotensin-converting enzyme inhibitors (ACE inhibitors) captopril and enalapril act by inhibiting the formation of angiotensin II from angiotensin I. They cross the placenta. No teratogenic effect has been proved for either drug. A high rate of fetal mortality has been reported in several animal species for captopril but the available clinical data are not sufficient to assess the role of the ACE inhibitors in perinatal mortality, intrauterine growth retardation, and fetal distress in humans. The fetal hemodynamic parameters may be affected by captopril administration to the mother: blood pressure falls, plasma renin activity increases, ACE activity decreases. As for most antihypertensive drugs, available information on the consequences of clonidine and ACE inhibitors in the neonate and the infant now seem sufficient to appreciate the risk in maternal therapy. In contrast, they are still insufficient considering their known effects on fetal hemodynamics, cardiovascular adaptation, and brain tolerance, with or without hypoxia, as well as for their possible long-term adverse effects.