FETOTOXICITY OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN PRIMATE PREGNANCY - A PROSPECTIVE, PLACEBO-CONTROLLED STUDY IN BABOONS (PAPIO-HAMADRYAS)

OBJECTIVES: Serious concerns have been raised about angiotensin-conver ting enzyme inhibition in pregnancy. The central question remains: doe s toxicity of angiotensin-converting enzyme inhibition pertain to preg nant humans? STUDY DESIGN: A prospective, placebo-controlled study was performed to investigate the effect of angiotensin-converting enzyme inhibition on pregnancy outcome in the baboon. Subjects (N = 12) recei ved active and placebo treatments sequentially in a crossover protocol . Data were analyzed with two-sample t tests, analysis of variance, Fi sher's exact test, or Kaplan-Meier survival analysis, where appropriat e. RESULTS: Chronic administration of enalapril (7.5 mg per day) from before conception achieved moderate but sustained angiotensin-converti ng enzyme inhibition as determined by repeated measures of renin-angio tensin system parameters (serum angiotensin-converting enzyme activity , plasma renin activity and plasma angiotensin I, angiotensin II, and aldosterone concentrations). Serum angiotensin-converting enzyme activ ity was significantly reduced throughout (<10 nmol.ml(-1).min(-1), p < 0.01), with significant increases in plasma renin activity and angiot ensin I (p < 0.01). Angiotensin II and aldosterone were maintained unc hanged compared with placebo. There was a significant incidence of fet al death or intrauterine growth retardation in fetuses exposed to enal april (eight of 13, zero on placebo, p < 0.01). When the definition of adverse pregnancy outcome was restricted to fetal death alone (four o f 13) the difference remained significant (p < 0.05). Maternal arteria l pressure was unchanged before conception, but a small and significan t fall (10 to 15 mm Hg, p < 0.01) was detected throughout pregnancy. T here was no fetal malformations. CONCLUSION: The study provides defini tive evidence for serious consequences of angiotensin-converting enzym e inhibition in pregnancy of high-order primates.