Infnts exposed to angiotensin converting enzyme inhibitors only during the first trimester are at increased risk for major congenital malformations, according to an article in the June 8 issue of the New England Journal of Medicine.

The current study is the first to find an adverse impact of this drug class on a fetus when taken only during the first trimester of pregnancy. Current warnings on drug use are applied only the second and third trimesters.

According to data from the USA National Ambulatory Medical Care Survey, in 1995 there were 1,426,220 prescriptions for angiotensin converting enzyme (ACE) inhibitors written in physicians’ offices for women ages 15 to 44 years. That number increased to 2,712,510 in 2002 for the same age group.

“These study findings raise a new and potentially important safety concerns for a woman who is taking ACE inhibitors before she or her doctor knows that she is pregnant,” said Carolyn M. Clancy, MD. “Clinicians who treat women of childbearing age and pregnant women should be aware of these new findings and consider whether to use other treatment options to control hypertension or kidney damage from diabetes.”

Researchers led by William O. Cooper, MD, MPH, of Vanderbilt Children’s Hospital examined data gathered from the Tennessee Medicaid program on 29,507 infants born between 1985 and 2000. Of the total study population, 209 infants were identified by researchers as having been exposed to the drug class during the first trimester, 202 had comparable exposure to other antihypertensive medications, and 29,096 had no maternal use of antihypertensive drugs.

The researchers found that major congenital malformations identified by vital records and hospital claims were diagnosed in 856, or 2.9 percent of infants, and that 203 infants had more than one malformation. Among infants exposed in the first trimester, the proportion born with major congenital malformations was 7.1 percent compared with 1.7 percent among infants exposed to other antihypertensive medications. The rate of major congenital malformations in the general population is about 3 percent.

The risk of a major congenital malformation among infants exposed during the first trimester was 2.71 times higher than in infants whose mothers did not use any hypertension medications. The increased overall risk seen with ACE inhibitors was due primarily to higher risks for cardiovascular and central nervous system malformations, including atria sepal defects, patent ducts arteries, hydrocephalus, and spinal bifida. The risk for all other types of malformations, including those of the musculoskeletal, gastrointestinal and genital systems, was not significantly increased by first-trimester exposure to ACE inhibitors.

“This study raises the important issue of a woman and her physician being aware of potential risks of medications that she might be taking before she becomes pregnant,” Cooper said. “While we believe the increased risk that we found in our study represents a true increase, further studies are needed to confirm these findings and to assess the risks of specific drugs and durations of exposure.”
Follow-up research has begun.