Fetotoxicity of angiotensin-converting enzyme inhibition in primate pregnancy: a prospective, placebo-controlled study in baboons (Papio hamadryas).
| Autor: | Harewood WJ; Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia., Phippard AF, Duggin GG, Horvath JS, Tiller DJ |
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| Jazyk: | angličtina |
| Zdroj: | American journal of obstetrics and gynecology [Am J Obstet Gynecol] 1994 Sep; Vol. 171 (3), pp. 633-42. |
| DOI: | 10.1016/0002-9378(94)90075-2 |
| Abstrakt: | Objectives: Serious concerns have been raised about angiotensin-converting enzyme inhibition in pregnancy. The central question remains: does toxicity of angiotensin-converting enzyme inhibition pertain to pregnant 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) received active and placebo treatments sequentially in a crossover protocol. Data were analyzed with two-sample t tests, analysis of variance, Fisher's exact test, or Kaplan-Meier survival analysis, where appropriate. Results: Chronic administration of enalapril (7.5 mg per day) from before conception achieved moderate but sustained angiotensin-converting enzyme inhibition as determined by repeated measures of renin-angiotensin system parameters (serum angiotensin-converting enzyme activity, plasma renin activity and plasma angiotensin I, angiotensin II, and aldosterone concentrations). Serum angiotensin-converting enzyme activity was significantly reduced throughout (< 10 nmol.ml-1.min-1, p < 0.01), with significant increases in plasma renin activity and angiotensin I (p < 0.01). Angiotensin II and aldosterone were maintained unchanged compared with placebo. There was a significant incidence of fetal death or intrauterine growth retardation in fetuses exposed to enalapril (eight of 13, zero on placebo, p < 0.01). When the definition of adverse pregnancy outcome was restricted to fetal death alone (four of 13) the difference remained significant (p < 0.05). Maternal arterial pressure was unchanged before conception, but a small and significant fall (10 to 15 mm Hg, p < 0.01) was detected throughout pregnancy. There was no fetal malformations. Conclusion: The study provides definitive evidence for serious consequences of angiotensin-converting enzyme inhibition in pregnancy of high-order primates. |
| Databáze: | MEDLINE |
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