CardioExchange Archive

Although the teratogenic properties of ACE inhibitors in the second and third trimesters of pregnancy are well-documented, the effects of their use in the first trimester have been unclear. Now a study suggests that hypertension itself, rather than ACE inhibitors or other antihypertensive drugs, is the likely cause of an increased risk for birth defects in this population.

In a paper published in BMJ, De-Kun Li and colleagues analyzed Kaiser Permanente data from 465,754 mother-infant pairs in Northern California from 1995 to 2008. After adjustment for other risk factors, mothers who used ACE inhibitors in the first trimester had an increased risk for congenital heart defects in their offspring only when compared with “normal” controls (i.e, mothers without hypertension). No significant elevation in risk was observed when ACE inhibitor users were compared either with women who used other antihypertensives or with hypertensive controls (i.e, women with untreated hypertension).

The authors concluded:

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.

In an accompanying editorial, Allen Mitchell writes that on the basis of this and previous studies “it is reasonable to conclude that exposure to ACE inhibitors during the first trimester poses no greater risk of birth defects than exposure to other antihypertensives.” He also discusses the implications of the finding that  hypertension can cause birth defects, and wonders if there are “physiological changes that might affect fetal development before they manifest as increased maternal blood pressure.”