ACE inhibitors may increase risk of birth defects

Women who are pregnant or may become pregnant should be given other treatment options.

ACE inhibitor use in the first trimester of pregnancy may cause birth defects.

The risk of birth defects from use during the second or third trimester has been fairly well documented, but this is new and troubling because it was previously assumed that the drugs would be safe in the first trimester, Raymond Woosley, MD, PhD, section editor of Cardiology Today's Cardiovascular Pharmacology section and president and CEO of the Critical Path Institute in Arizona, told Cardiology Today.

William Cooper, MD, associate professor of pediatrics at Vanderbilt University Medical Center, led a study of 29,507 infants enrolled in Tennessee Medicaid. The results were published in a recent New England Journal of Medicine.

William Cooper

“Any woman who is taking ACE inhibitors, who is planning to become pregnant or likely to become pregnant, should really talk to her doctor about other blood pressure medications,” Cooper told Cardiology Today.

Woosley, who was not involved in the study, agreed. Cooper said that of the 47 different medications indicated for lowering blood pressure, eight have not been associated with birth defects when used by pregnant women.

Safer options

In an accompanying editorial in the New England Journal of Medicine, Jan M. Friedman, MD, PhD, professor of medical genetics at the University of British Columbia, listed the eight available options: chlorothiazide, chlorthalidone, hydrochlorothiazide, atenolol, acebutolol, pindolol, nifedipine and reserpine.

Although these drugs have not been associated with birth defects, there are other concerns, Friedman said, and more research is needed in this population group.

“Because of our ignorance, some pregnant women may not receive treatments that would benefit their own health and that of the fetus,” Friedman wrote.

Woosley agreed with Friedman that more research is needed into drug use among pregnant women.

“The basic message from the FDA has always been ‘don’t get pregnant because we often don’t have any data on what will happen with your drugs,’” Woosley said. “People do get pregnant, and they get concerned. There is a further concern that people would terminate a pregnancy based on a fear of birth defects without confirmation that the fetus has been affected.”

ACE inhibitors

In the current study, researchers identified infants for whom there was no evidence of maternal diabetes. Of the original cohort of 29,507 infants, they noted 209 who had been exposed to ACE inhibitors during the first trimester and 202 who had been exposed to another antihypertensive agent.

Researchers identified major congenital malformations from linked vital records and hospitalization claims during the first year of life and confirmed this by review of medical records.

Compared with infants who had no exposure to antihypertensive agents, those who were exposed to ACE inhibitors in the first trimester had a nearly threefold risk of congenital malformations (RR=2.71; 95% CI, 1.72-4.27).

When congenital malformations were examined by type, there was a nearly fourfold increased risk of cardiovascular malformations (RR=3.72; 95% CI, 1.89-7.30) and a more than fourfold risk of central nervous system malformations (RR=4.39; 95% CI, 1.37-14.02).

Other antihypertensive medications did not confer increased risk (RR=.66; 95% CI, 0.25-1.75). – by Jeremy Moore

For more information:

• Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354:2443-2451.
• Friedman JM. ACE inhibitors and congenital abnormalities. N Engl J Med. 2006;354:2498-2500.