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ACE Inhibitors Are Teratogenic in the First Trimester

Specifically, these drugs were associated with increased infant risks for cardiovascular and nervous system anomalies.

ACE inhibitors, long known to be teratogenic when used in the last two trimesters of pregnancy, have been considered safe in the first trimester. However, this assumption has been based on relatively limited data. These researchers analyzed medication-use and other data from Medicaid recipients in Tennessee to assess whether first-trimester exposure to ACE inhibitors is associated with congenital malformations.

Of 29,507 analyzed births, 411 involved exposure to antihypertensive drugs only during the first trimester (209 to ACE inhibitors, 202 to other antihypertensives not specified in the article). Overall, 856 infants (2.9%) had congenital malformations that were not related to a chromosomal defect or a clinical genetic syndrome.

Congenital malformation rates were 7.1% among infants exposed to ACE inhibitors only during the first trimester, 1.7% among infants with first-trimester exposure to other antihypertensive drugs, and 2.6% among infants not exposed to antihypertensives. After adjustment for potential confounders, the risk ratio for first-trimester ACE-inhibitor exposure was 2.71 (95% CI, 1.72–4.27), compared with no first-trimester antihypertensive exposure. Most malformations were in the cardiovascular and nervous systems. Antihypertensive drugs other than ACE inhibitors were not associated with an increased adjusted risk for malformations.

Comment: These data raise a major concern for women of childbearing age treated with ACE inhibitors. With their pregnant patients, clinicians need to weigh the potential harm of not treating chronic conditions such as hypertension against the potential teratogenicity of drugs used to treat those conditions, bearing in mind that for many drugs teratogenicity has not been well studied. The findings also emphasize the need for safety surveillance of medications after they are approved.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology July 5, 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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• Medline abstract (Free)

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

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• Medline abstract (Free)