Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study

Objective To examine a reported association between use of angiotensin converting enzyme (ACE) inhibitors during the first trimester and risk of malformations in offspring. Design A population based, retrospective cohort study linking automated clinical and pharmacy databases including comprehensive electronic medical records. Participants Pregnant women and their live born offspring (465 754 mother-infant pairs) in the Kaiser Permanente Northern California region from 1995 to 2008. Main outcome measure Congenital malformation in live births. Results The prevalence of ACE inhibitor use in the first trimester only was 0.9/1000, and the use of other antihypertensive medications was 2.4/1000. After adjustment for maternal age, ethnicity, parity, and obesity, use of ACE inhibitors during the first trimester only seemed to be associated with increased risk of congenital heart defects in offspring compared with normal controls (those with neither hypertension nor use of any antihypertensives during pregnancy) (15/381 (3.9%) v 6232/400 021 (1.6%) cases, odds ratio 1.54 (95% confidence interval 0.90 to 2.62)). A similar association was observed for use of other antihypertensives (28/1090 (2.6%) cases of congenital heart defects, odds ratio 1.52 (1.04 to 2.21)). However, compared with hypertension controls (those with a diagnosis of hypertension but without use of antihypertensives) (708/29 735 (2.4%) cases of congenital heart defects), neither use of ACE inhibitors or of other antihypertensives in the first trimester was associated with increased congenital heart defects risk (odds ratios 1.14 (0.65 to 1.98) and1.12 (0.76 to 1.64) respectively). Conclusions Maternal use of ACE inhibitors in the first trimester has a risk profile similar to the use of other antihypertensives regarding malformations in live born offspring. The apparent increased risk of malformations associated with use of ACE inhibitors (and other antihypertensives) in the first trimester is likely due to the underlying hypertension rather than the medications.