Cooper WO et al. (2006) Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 354: 2443–2451

Women should not be given angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy, as these drugs have been linked with an increased risk of fetopathy. Data on the use of ACE inhibitors in the first trimester are sparse, however, and researchers in the US have addressed this issue using data from 29,507 births recorded in the Tennessee Medicaid database.

In total, 411 infants had been exposed to antihypertensive medications during the first trimester alone; 209 of these had been exposed to ACE inhibitors and 202 to other hypertensive medications. Overall, 856 infants were diagnosed with at least one major congenital malformation not related to a chromosomal defect or a clinical genetic syndrome. The most common types of malformation were cardiovascular, musculoskeletal and gastrointestinal malformations, affecting 305, 195 and 119 infants, respectively. The risk of major congenital malformation was over twofold higher in infants who had been exposed to ACE inhibitors in the first trimester alone than in those not exposed to antihypertensive medications (risk ratio 2.71). This increased risk results mainly from higher risks of cardiovascular and central nervous system malformations (risk ratios 3.72 and 4.39, respectively); other malformations were not significantly higher in infants exposed to ACE inhibitors. Exposure to antihypertensive medications other than ACE inhibitors in the first trimester had no effect on the risk of any major congenital malformation.

The authors conclude that ACE inhibitors are associated with an increased risk of a major congenital malformation and should not be used during pregnancy.