enalapril and Fetal-Death

To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation.. Relevant English-language articles identified through a Medline search and bibliographies found in recent articles.. Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy.. The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy.

Topics: Abnormalities, Drug-Induced; Animals; Blood Pressure; Captopril; Ductus Arteriosus, Patent; Enalapril; Female; Fetal Death; Fetus; Goats; Kidney; Maternal-Fetal Exchange; Oligohydramnios; Pregnancy; Rabbits; Regional Blood Flow; Renal Insufficiency; Risk Factors; Sheep; Uterus; Vascular Resistance

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?. 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.. 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.. The study provides definitive evidence for serious consequences of angiotensin-converting enzyme inhibition in pregnancy of high-order primates.

Topics: Aldosterone; Analysis of Variance; Angiotensin I; Angiotensin II; Animals; Blood Pressure; Enalapril; Female; Fetal Death; Fetal Growth Retardation; Papio; Peptidyl-Dipeptidase A; Pregnancy; Pregnancy Outcome; Prospective Studies; Random Allocation; Renin

Topics: Adult; Enalapril; Female; Fetal Death; Fetal Diseases; Humans; Polycystic Kidney Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Diagnosis; Ultrasonography, Prenatal

Topics: Abortion, Spontaneous; Captopril; Ductus Arteriosus, Patent; Enalapril; Female; Fetal Death; Humans; Hypertension; Infant, Newborn; Infant, Small for Gestational Age; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third