Fetal risk from angiotensin converting enzyme inhibitors in the first trimester

In 1980, published animal data in The Lancet flagged concerns with the angiotensin converting enzyme (ACE) inhibitor captopril. ¹ Publications on the safety of ACE inhibitors followed in the 1980s.

By 1993, ACE inhibitor fetopathy had been described in the offspring of patients who took these drugs in the second and third trimesters. The adverse outcomes were deliberately called fetopathy rather than teratogenicity at that time. ²

A 2006 report raised further concerns by demonstrating an association of ACE inhibitors used in the first trimester of pregnancy with an increased rate of birth defects, in particular cardiac malformations and neural tube defects. Other antihypertensive drugs were not associated with increased risks in birth defects. ³

However, in 2011 Li et al., in a retrospective cohort study with a much larger population base and a more ethnically diverse population, did not confirm the reported findings. The study showed that hypertension itself appears to be a modest risk for birth defects, particularly cardiac. ⁴ Similar findings were reported in a smaller Swedish cohort study ⁵ and a large case-control US study. ⁶