Pregnancy and ACE inhibitors

Treating hypertension on pregnancy sometimes feels a little like going back in time. As Nate posted previously, the list of anti-hypertensives that are considered safe in pregnancy is relatively short – first line agents include labetalol, hydralazine, methyldopa and some calcium channel blockers, while beta-blockers and diuretics are relatively contraindicated and ACEi and ARBs are definitely contraindicated. ACEi have been associated with a constellation of fetal injuries when used in later pregnancy while a study published in 2006 suggested that they were associated with fetal malformations when used in the first trimester. Given the prevalence of hypertension in the general population and the ubiquity of ACEi, this lead to some understandable anxiety about whether these classes of drugs should be prescribed at all to women of child-bearing potential.

However, two recent studies published in the BMJ and the Journal of Obstetrics and Gynecology have challenged this orthodoxy. The first is a large registry study while the second is a meta-analysis of all studies of ACEi in early pregnancy. These two large studies found that although the risk for fetal malformations was higher than controls with first trimester use of ACEi, there was a similar increased risk associated with the use of any other class of anti-hypertensive and in women with untreated hypertension. There was no excess risk of ACEi over these other groups. This suggests that it is the hypertension itself that is causing the increased risk of malformations rather than any effect of an individual medication. It is important to note that the previously documented association between fetal malformations and the use of ACEi in the second and third trimesters was confirmed in the BMJ study. This indicates that the drugs are not safe for use throughout pregnancy and should be stopped when a woman becomes pregnant. That said, it should bring some relief to mothers who have conceived while taking an ACEi that they have not done any inadvertent harm to their children.

I recommend this excellent editorial on the topic