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ACE Inhibitors and Birth Defects: Unsafe in Any Trimester

Treatment with ACE inhibitors increases risk for major malformations when used in the first trimester as well as later in pregnancy.

Angiotensin-converting-enzyme (ACE) inhibitors (see Table 1) are popular and effective antihypertensives that have long been contraindicated in the second and third trimesters of pregnancy due to an elevated risk for fetopathy. In this study based on Tennessee Medicaid records, investigators linked birth data with maternal, infant, and pharmacy records to assess risk for major congenital anomalies associated with first-trimester exposure to ACE inhibitors. Infants with the following prenatal histories were included in the study: ACE-inhibitor exposure in the first trimester only (209 infants), exposure to other antihypertensives in the first trimester only (202 infants), or no antihypertensive exposure throughout pregnancy (29,096 infants).

Among infants who had ACE-inhibitor exposure in the first trimester only, the adjusted proportion with major congenital anomalies was 7.1%. These infants had a significantly higher risk for major congenital malformation than did infants who had no prenatal exposure to antihypertensive medications (risk ratio, 2.71). This increased risk manifested itself mainly as elevated risks for malformations of the cardiovascular system (RR, 3.72) and central nervous system (RR, 4.39). A post hoc analysis also revealed an increased risk for renal anomalies (RR, 9.32). In general, use of other antihypertensives during the first trimester alone was not associated with an increased risk for malformations of any type.

Comment: As the indications for ACE inhibitors expand, their use has increased among U.S. women of childbearing age. An editorialist notes that the findings of this study should be considered exploratory. However, given that many other antihypertensives are considered safe for use during pregnancy (e.g., thiazides, ß-blockers, methyldopa, and nifedipine), these findings provide support for minimizing the use of ACE inhibitors in women who are, or might become, pregnant. Women who use ACE inhibitors during the first trimester should be offered prenatal diagnosis, counseling, and options for changing medications.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health July 13, 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)