Infants born to mothers who took angiotensin converting enzyme (ACE) inhibitors during the first trimester of pregnancy had an increased risk of major congenital malformations compared with infants whose mothers didn't take these drugs. The study, jointly funded by the Agency for Healthcare Research and Quality (HS10384) and the Food and Drug Administration (FDA), is the first to find an adverse impact of ACE inhibitors on a fetus when taken only during the first trimester of pregnancy.
ACE inhibitors, a class of medications primarily used to lower blood pressure and/or to preserve kidney function in people with diabetes, already carry an FDA "black box" warning stating that they can cause injury and even death to the developing fetus when used during the second and third trimesters of pregnancy. The warning states that use of ACE inhibitors should be discontinued as soon as possible when pregnancy is detected.
The study was conducted by researchers at the AHRQ-sponsored Vanderbilt University Center for Education and Research on Therapeutics (CERTs) in Nashville. The mission of the CERTs is to conduct research and provide education that will advance the best use of therapeutics (drugs, medical devices, and biological products). The program is administered as a cooperative agreement by AHRQ, in consultation with the FDA.
Researchers 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 as having been exposed to ACE inhibitors 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 to ACE inhibitors 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—or 3 infants out of every 100 pregnancies.
The chances of a major congenital malformation among infants exposed to ACE inhibitors during the first trimester were nearly 3 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 atrial septal defect (hole in the wall that separates the two upper chambers of the heart), patent ductus arteriosus (an open blood vessel that causes blood to flow into the baby's lungs), hydrocephalus, and spina 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.
More details are in "Major congenital malformations after first-trimester exposure to ACE inhibitors," by William O. Cooper, M.D., M.P.H., Sonia Hernandez-Diaz, M.D., Dr.P.H., Patrick G. Arbogast, Ph.D., and others, in the June 8, 2006, New England Journal of Medicine 354, pp. 2443-2451.