Can ACE Inhibitors be used during pregnancy?

1.

Elsevier ClinicalKey Drug Class Overview

Content last updated: June 0, 2020.

Do not use enalaprilat in pregnant women. Angiotensin-converting enzyme (ACE) inhibitors can cause fetal and neonatal injury, such as hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death when administered to pregnant women during the second and third trimesters[33903].

2.

Angiotensin-Converting Enzyme (ACE) Inhibitors, Elsevier ClinicalKey Drug Class Overview

Content last updated: July 1, 2012.

When pregnancy is detected, discontinue ACE inhibitor therapy as soon as possible. Use of medications that affect the renin-angiotensin system, such as ACE inhibitors, during the second or third trimesters reduce fetal renal function, increase fetal and neonatal death, and cause fetal and neonatal injury such as hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Anhydramnios and oligohydraminos have also been reported. Women of childbearing age should be made aware of these harmful effects and consideration given to using another drug class.

3.

Elsevier ClinicalKey Drug Monograph

Content last updated: April 1, 2024.

Pregnancy When used during human pregnancy during the second and third trimesters, angiotensin-converting enzyme (ACE) inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, monopril should be discontinued as soon as possible. Women of child-bearing age should be made aware of the potential risk and ACE inhibitors should only be given after careful counseling and consideration of individual risks and benefits. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible and monitoring of the fetal development should be performed on a regular basis. Rarely (probably less often than once per every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the pregnant women should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. The reported adverse fetal and neonatal effects (e.g., hypotension, neonatal skull hypoplasia and craniofacial deformation, fetal limb contractures, hypoplastic lung development, anuria, oligohydramnios, reversible or irreversible renal failure, and death) have been reported during ACE inhibitor exposure during the second and third trimesters. An observational study based on Tennessee Medicaid data reported that the risk of congenital malformations is significantly increased during first-trimester exposure to ACE inhibitors. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in babies exposed to ACE inhibitors during the first trimester, in those exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Newborns born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. Further evaluation of teratogenicity data associated with ACE inhibitor exposure during pregnancy is ongoing. Closely observe neonates with histories of in utero exposure to monopril for hypotension, oliguria, and hyperkalemia.

Contraindications And Precautions When used during human pregnancy during the second and third trimesters, angiotensin-converting enzyme (ACE) inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, fosinopril should be discontinued as soon as possible. Women of child-bearing age should be made aware of the potential risk and ACE inhibitors should only be given after careful counseling and consideration of individual risks and benefits. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible and monitoring of the fetal development should be performed on a regular basis. Rarely (probably less often than once per every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the pregnant women should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. The reported adverse fetal and neonatal effects (e.g., hypotension, neonatal skull hypoplasia and craniofacial deformation, fetal limb contractures, hypoplastic lung development, anuria, oligohydramnios, reversible or irreversible renal failure, and death) have been reported during ACE inhibitor exposure during the second and third trimesters. An observational study based on Tennessee Medicaid data reported that the risk of congenital malformations is significantly increased during first-trimester exposure to ACE inhibitors. However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in babies exposed to ACE inhibitors during the first trimester, in those exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Newborns born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. Further evaluation of teratogenicity data associated with ACE inhibitor exposure during pregnancy is ongoing.

4.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Pregnancy When used during human pregnancy during the second and third trimesters, altace, like all angiotensin-receptor converting enzyme (ACE) inhibitors, can cause injury and even death to the developing fetus. When pregnancy is detected, altace should be discontinued as soon as possible. Women of child-bearing age should be made aware of the potential risk and altace should only be given after careful counseling and consideration of individual risks and benefits. When used during the second and third trimesters, drugs that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Other potential neonatal adverse effects include skull hypoplasia, anuria, and hypotension. Retrospective data indicate that first trimester use of ACE inhibitors has been associated with a potential risk of birth defects. However, a large observational study (n = 465,754) found that the risk of birth defects was similar in babies exposed to ACE inhibitors during the first trimester, in those exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Newborns born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. In rare cases when another antihypertensive agent can not be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue altace unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe neonates with histories of in utero exposure to altace for hypotension, oliguria, and hyperkalemia.

5.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Pregnancy When used in pregnancy during the second and third trimesters, lotensin, like all angiotensin-converting enzyme (ACE) inhibitors, can cause injury and even death to the developing fetus. When pregnancy is detected, lotensin should be discontinued as soon as possible. Women of child-bearing age should be made aware of the potential risk, and lotensin should only be given after careful counseling and consideration of individual risks and benefits. When used during the second and third trimesters, drugs that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Other potential neonatal adverse effects include skull hypoplasia, anuria, and hypotension. Retrospective data indicate that first-trimester use of ACE inhibitors has been associated with a potential risk of birth defects. However, a large observational study (n = 465,754) found that the risk of birth defects was similar in babies exposed to ACE inhibitors during the first trimester, in those exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated. Newborns born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. In rare cases when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue lotensin unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe neonates with histories of in utero exposure to lotensin for hypotension, oliguria, and hyperkalemia.

6.

Food and Drug Administration (DailyMed).

Publish date: October 1, 2010.

Warnings At these doses, fetotoxicity expressed as a decrease in average fetal weight occurred in both species. No fetotoxicity occurred at lower doses; 30/10 mg/kg/day of enalapril-hydrochlorothiazide in rats and 10/10 mg/kg/day of enalapril-hydrochlorothiazide in mice. When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, enalapril maleate and hydrochlorothiazide tablets should be discontinued as soon as possible (see Enalapril Maleate, Fetal/Neonatal Morbidity and Mortality , below). Enalapril Maleate Fetal/Neonatal Morbidity and Mortality ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. In a published restrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death.

7.

Food and Drug Administration (DailyMed).

Publish date: February 2, 2023.

Warnings In most cases, proteinuria subsided or cleared within six months whether or not captopril was continued. Parameters of renal function, such as BUN and creatinine, were seldom altered in the patients with proteinuria. Hypotension : Excessive hypotension was rarely seen in hypertensive patients but is a possible consequence of captopril use in salt/volume depleted persons (such as those treated vigorously with diuretics), patients with heart failure or those patients undergoing renal dialysis. (See PRECAUTIONS: Drug Interactions .) Fetal/Neonatal Morbidity and Mortality : ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE-inhibitor exposure. These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed.

Warnings Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of captopril as soon as possible. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, captopril should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. While captopril may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children. Peritoneal dialysis is not effective for removing captopril; there is no information concerning exchange transfusion for removing captopril from the general circulation.

8.

Whelton PK, Carey RM, Aronow WS, et al. Journal of the American College of Cardiology. 2018;71(19):e127-e248. doi:10.1016/j.jacc.2017.11.006.

Publish date: May 2, 2018.

Hypertension in pregnancy has special requirements (see Section 10.2.2). Women with hypertension who become pregnant should not be treated with ACE inhibitors, ARBs, or direct renin inhibitorsS10.2.2-4, S10.2.2-5, S10.2.2-6. BP usually declines during the first trimester of pregnancy and then slowly rises. Hypertension management during pregnancy includes 4 general areas: 1) the newly pregnant mother with existing hypertension; 2) incident hypertension; 3) preeclampsia (a dangerous form of hypertension with proteinuria that has the potential to result in serious adverse consequences for the mother [stroke, HF] and fetus [small for gestational age, premature birth]); and 4) severe hypertension, often in the setting of preeclampsia, requiring urgent treatment to prevent HF, stroke, and adverse fetal outcomes. Hypertension during pregnancy and preeclampsia are recognized as risk factors for future hypertension and CVD S10.2.2-7, S10.2.2-8, S10.2.2-9. BP management during pregnancy is complicated by the fact that many commonly used antihypertensive agents, including ACE inhibitors and ARBs, are contraindicated during pregnancy because of potential harm to the fetus S10.2.2-2, S10.2.2-3. The goal of antihypertensive treatment during pregnancy includes prevention of severe hypertension and the possibility of prolonging gestation to allow the fetus more time to mature before delivery. There are 3 Cochrane database reviews of treatment for mild-to-moderate hypertension during pregnancy S10.2.2-10, S10.2.2-11, S10.2.2-12. With regard to the treatment of mild-to-moderate hypertension (SBP of 140–169 or DBP of 90–109 mm Hg), antihypertensive treatment reduces the risk of progression to severe hypertension by 50% compared with placebo but has not been shown to prevent preeclampsia, preterm birth, small for gestational age, or infant mortality. Beta blockers and CCBs appear superior to alpha-methyldopa in preventing preeclampsia (S10.2.2-10).