Why ACE Inhibitors and ARBs Should Be Avoided During Pregnancy

Use During First Trimester Increases Birth Defects

While most drugs used to treat hypertension can be taken safely in women who are pregnant, two closely related categories of blood pressure medication should be avoided. These are angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARB) drugs. Both types of drugs pose serious risks to the developing baby, and should not be used at any time during pregnancy.​

Pregnant woman reading and rubbing her belly on couch
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Understanding ACE Inhibitors and ARBs

ACE inhibitors and ARB drugs both work by blocking components of the renin-angiotensin pathway, one of the body’s major systems for modulating blood pressure. By partially blocking some of the molecules mediated by the renin-angiotensin pathway, ACE inhibitors and ARBs can reduce the blood pressure in most patients with hypertension.

Why These Drugs Should Not Be Used During Pregnancy

A study from Tennessee in 2006 first identified a problem with ACE inhibitors in pregnant women. In nearly 30,000 births from a database maintained by Tennessee Medicaid, 411 infants had been exposed to antihypertensive drugs during the first trimester. Those who were exposed to ACE inhibitors (209 babies) had a risk of birth defects that was almost three times higher than those not exposed to ACE inhibitors: nine had cardiovascular malformations, three had central nervous system malformations, and six had other kinds of birth defects.

Overall, 7% of infants exposed to ACE inhibitors in the first trimester had some form of birth defect, compared to a 2.6% risk among babies who had no exposure to any antihypertensive medication. Babies who had exposure to antihypertensive drugs other than ACE inhibitors showed no increase in risk.

Since that initial analysis, several other studies have confirmed that ACE inhibitors during pregnancy are associated with a significantly increased risk of birth defects and other problems.

In addition, subsequent studies have shown that the use of ARBs during early pregnancy is associated with the same kinds of birth defects. If anything, the risk with ARBs appears to be even higher than it is with ACE inhibitors.

Usage of ACE inhibitors and ARBs during the second and third trimesters of pregnancy also causes serious problems, though of a different type.

Used later in pregnancy, these drugs cause serious kidney problems in the baby, including impaired renal function or kidney failure. Late-pregnancy use of these drugs may also cause low birth weight, growth retardation, and premature delivery.

The Bottom Line

Because of the serious risks posed to babies whose mothers take ACE inhibitors or ARBs at any time during pregnancy, and because several other classes of medications are safe and generally effective at treating hypertension in pregnant women, most doctors recommend that these drugs not be used at all in women of childbearing age.

If treating hypertension adequately cannot be accomplished without adding ACE inhibitors or ARBs, women of childbearing age should take precautions to avoid pregnancy. They should stop taking their medication any time their menstrual period is delayed by more than 48 hours, and perform a pregnancy test.

Sources
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  • Bullo M, Tschumi S, Bucher BS, et al. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. Hypertension 2012; 60:444.
  • Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006; 354:2443-24511.
  • Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006; 354:2498-2500.
Richard N. Fogoros, MD

By Richard N. Fogoros, MD
Richard N. Fogoros, MD, is a retired professor of medicine and board-certified in internal medicine, clinical cardiology, and clinical electrophysiology.