No Increase in Birth Defects with First-Trimester ACE Inhibitors

Exposure to angiotensin-converting enzyme (ACE) inhibitors during the first trimester of pregnancy does not increase the risk of congenital malformations, reports the British Medical Journal.

The researchers analyzed data on 465,744 mother–infant pairs in the Kaiser Permanente Northern California region between 1995 and 2008. Linked clinical and pharmacy data were used to evaluate the relationship between maternal ACE inhibitor use during the first trimester and the risk of congenital malformations in live-born offspring.

The rate of ACE inhibitor use by pregnant women dropped sharply from 0.9/1000 in the first trimester to only 0.1/1000 in the second or third trimester. The prevalence of treatment with other antihypertensive agents was 2.4/1000 and 26.5/1000, respectively.

Women who used ACE inhibitors during the first trimester had a 3.9 percent rate of congenital heart defects in their offspring compared with 1.6 percent for women without hypertension or antihypertensive medication use. No significant association extisted after adjustment for age, ethnicity, parity, and obesity. The rate of congenital heart defects among infants born to mothers using other antihypertensive drugs was 2.6 percent—not significantly different from the 2.4 percent rate for women who had hypertension but did not take antihypertensive drugs.

The ACE inhibitors have well-recognized fetal toxic effects during the second or third trimester. Addressing concerns raised by recent studies, the new results show no significant increase in congenital malformations associated with first-trimester exposure to ACE inhibitors. Any apparent increase in risk likely reflects the effects of hypertension itself rather than of antihypertensive medications. [Li DK, et al. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011; 343:d5931.]

December 2011 (Vol. 3, Number 12)