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Safety of First-Trimester Exposure to ACE Inhibitors

Medicaid data on nearly 30,000 births showed a significant increase in risk for major congenital anomalies with first-trimester exposure.

Angiotensin-converting–enzyme (ACE) inhibitors are contraindicated during the second and third trimesters of pregnancy because their use increases risk for various fetal anomalies. In this study, researchers used Tennessee's Medicaid database to determine whether use of ACE inhibitors is safe during the first trimester.

The researchers identified nearly 30,000 births that occurred among nondiabetic mothers between 1985 and 2000. During the first trimester, ACE inhibitors were prescribed to 209 mothers, antihypertensive drugs other than ACE inhibitors were prescribed to 202 mothers, and no antihypertensive drugs were prescribed to 29,096 mothers. Major congenital malformations occurred in 7.1% of infants with first-trimester exposure to ACE inhibitors, 1.7% of infants with exposure to other antihypertensive drugs, and 2.6% of infants with no antihypertensive drug exposure. After adjustment for confounders, risk for major congenital malformations with first-trimester ACE inhibitor exposure was increased significantly compared with no drug exposure (risk ratio, 2.7). Cardiovascular malformations accounted for about half of the anomalies.

Comment: These results raise serious concern about early fetal exposure to ACE inhibitors. Should clinicians generally avoid prescribing ACE inhibitors to women of childbearing age, as many pregnancies are unplanned? In considering this question, an editorialist notes that a few antihypertensive agents (e.g., thiazides, several ß-blockers, nifedipine) are considered "unlikely to pose a substantial teratogenic risk," but that data on teratogenicity are "no better than fair," even for these agents. Methyldopa also is considered safe for use during pregnancy.

— Allan S. Brett, MD

Published in Journal Watch General Medicine June 27, 2006

Citation(s):

Cooper WO et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006 Jun 8; 354:2443-51.

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Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006 Jun 8; 354:2498-500.

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• Medline abstract (Free)