Clinical implications of increased congenital malformations after first trimester exposures to angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors are some of the most frequently prescribed antihypertensives in the United States. These agents are contraindicated during the second half of pregnancy because prior studies have demonstrated that use of ACE inhibitors late in pregnancy can cause oligohydramnios, fetal growth restriction, skull defects, infant anuria and renal failure, and death. Interestingly, little was known about the effects of ACE inhibitors when taken early during pregnancy. The purpose of the ACE Inhibitors in Early Pregnancy study was to clarify the safety of the use of ACE inhibitors during pregnancy by conducting an epidemiologic study using a large Medicaid database in which medications prescribed for pregnant women as a part of routine care and infant outcomes were studied. In the study, among 209 infants with first trimester exposure to ACE inhibitors, 7.1% had any major congenital malformation. Compared with 29,096 infants with no exposure to any antihypertensive medication, among whom 2.6% had any major congenital malformation, the adjusted risk of major congenital malformations was increased more than 2-fold. The risks of any congenital malformations and risks of specific organ system malformations, including cardiac malformations, were not increased in 202 infants with first trimester exposure to other antihypertensives when compared with infants with no antihypertensive exposure. Although this was an exploratory study whose findings should be confirmed, there are some important clinical insights that can be drawn from the study's conclusions. Further information on the pregnancy risks of ACE inhibitors and almost every other medication potentially used by pregnant women is needed. Thus, well-controlled studies to identify these risks should be undertaken. Until such information is available, alternative medications to ACE inhibitors should be considered in women of child-bearing age who are pregnant or who are likely to become pregnant while taking the medication.