Angiotensin‐converting enzyme inhibitors, an embryopathic class of drugs with unique properties: Information for clinical teratology counselors

Abstract

LITERATURE CITED Barr, M. (1990) Fetal effects of angiotension converting enzyme inhibitor (abstr.). Teratology, 41 537. Batastini, G., R.N. Infurna, KlV. Wimbert, M.A. Youreneff, E.T. Yau, and V.M. Triana (1988) Teratologic evaluation of CGS 16617, an angiotensin converting enzyme inhibiting agent. Teratology, 37:445. Binder, N.D., J.J. Faber, and D.F. Anderson (1989) The effect of captopril on blood pressure, uterine blood flow, and uterine oxygen consumption in the pregnant rabbit. Clin. Reg., 37:176A. Boutroy, M.J. (1989) Fetal effects of maternally administered clonidine and angiotension-converting enzyme inhibitors. Dev. Pharmacol. Ther., 13:199-204. Boutroy, M.J., P. Vert, B. Huralt de Ligny, and A. Miton

The effect of antihypertensive drugs on the fetus

“…With some exceptions, 38 despite early case reports supporting the safety of ACEIs in pregnancy, the literature is generally not in favour of using ACEIs because of associated severe fetal and neonatal disease. 39 A number of reviews and reports addressed to clinical tetralogy counsellors cited oligohydramnios and/or neonatal anuria, pulmonary hydroplasia, mild to severe intrauterine growth retardation, and fetal death associated with ACEIs. Persistent anuria in neonates was attributed to maternal intake of captopril 40 and to a battery of antihypertensive drugs including enalapril.…”

“…Brent 39 considered it important to alert physicians to the possibility of fetal and neonatal disease following transplacental passage of captopril, especially since a report suggesting that captopril is not teratogenic 49 raised the likelihood of physicians prescribing it during pregnancy.…”

“…Although there is agreement that ACEIs can pose a risk to the fetus, 39 there is controversy over the timing and duration of exposure in relation to fetal risk and the magnitude of the risk during the unsafe stages. While an editorial in The Lancet in 1989 50 cautioned that most of the pregnant women reported in the various studies were also receiving other drugs, there is no question that oligohydramnios, fetal death, neonatal anuria, intrauterine growth retardation and fetal calvarial hypoplasia are direct effects of ACEIs on the fetus.…”

The Use of Angiotensin Converting Enzyme Inhibitors during the First Trimester of Pregnancy

“…The first adverse effects on a fetus were reported in 1981 and these related to exposure during trimesters two and three [7,8]. ACEIs are known to cross the placenta [9][10][11][12]. It is now known that when administered mid-late pregnancy, ACEIs can impair fetal development through inducing fetal hypotension, decreasing uterine, umbilical, and renal blood flow [13].…”

“…It is now known that when administered mid-late pregnancy, ACEIs can impair fetal development through inducing fetal hypotension, decreasing uterine, umbilical, and renal blood flow [13]. This can induce oligohydramnios, growth reduction, hypocalvaria, hypotension, neonatal renal failure and death [12][13][14][15]. Since 1992, the U.S. Food and Drug Administration has required a warning on all ACEIs regarding their fetotoxic effects when used during trimesters two and three [16,17].…”