ACE Inhibitors May Increase Risk of Birth Defects

New research suggests fetal exposure during early pregnancy to angiotensin-converting enzyme (ACE) inhibitors, a class of drug commonly prescribed to reduce blood pressure, increases the risk of major birth defects.¹

“Exposure to ACE inhibitors during the first trimester cannot be considered safe and should be avoided,” concludes lead researcher William Cooper, MD, MPH, of Vanderbilt University in Nashville, Tenn.

The risks of ACE inhibitors during the second and third trimesters of pregnancy are known and acknowledged in a Food and Drug Administration “black box” warning on the label. But this study raises a question about an agent that has not previously been associated with adverse outcomes when used during the first trimester.

The researchers looked at the Tennessee Medicaid records of 29,507 infants born in the years 1985–2000. The team restricted its study to infants whose mothers had no evidence of diabetes, as diabetes itself is strongly linked with a risk of birth defects, and many patients with diabetes are prescribed ACE inhibitors. The records included those of 411 babies who were exposed to antihypertensive drugs in the first trimester alone; of those, 209 were exposed to ACE inhibitors only.

Seven percent of infants whose mothers took ACE inhibitors in the first trimester had significant birth defects. These babies were more than twice as likely to have major cardiovascular and central nervous system malformations as those exposed to no antihypertensive drugs. Exposure to other antihypertensive drugs during the first trimester alone “did not confer an increased risk,” the researchers found.

“From this analysis, it looks like there may be reason for concern about the use of ACE inhibitors during early pregnancy,” says Michael P. Diamond, MD, associate chair of obstetrics and gynecology at Wayne State University in Detroit. “I wouldn't call it a definitive study. There needs to be further follow-up to see if in different patient populations this observation continues to hold. These are the sorts of studies you could do with a good patient database.

“It will be important to hear what the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine will say once they've had a chance to scrutinize and discuss these reports,” Diamond continues. “Is it something about women with hypertension that causes increased risk, and they happen to be using this drug? This study suggests that is not the case, but it would have to be looked at.” ▪