ACE inhibitors/ARBs not major human teratogens but associated with an increased risk for miscarriage: Study
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. The aim of this study was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited.
Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P <0.001 for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P < 0.001).
Establishing the safety of ACE inhibitors and ARBs after first trimester exposure is important for a number of reasons. Most notably is that women continue to need effective treatment for their existing chronic hypertension and that a large number of pregnancies will be exposed inadvertently to these agents. Accurate information on the safety of these agents will assist women and their health care practitioners in making rational choices about appropriate treatment. While there is a consensus that ACE inhibitor/ARBs should be discontinued when pregnancy is diagnosed to prevent fetal renal damage and associated complications, women often do not plan pregnancy, and fetal exposure in the first trimester is inevitable.
The study results are reassuring and consistent with a growing body of evidence that did not find an apparent increased risk for malformations among liveborns following exposure to ACE inhibitor/ARBs in early pregnancy. In fact, the rates of malformations were comparable to our healthy comparator group. Given that the ACE/ARBs are known to affect the fetal renin-angiotensin axis which becomes active in the second trimester, it is not surprising that to date, adverse fetal effects of these agents have been shown only after exposures which continued into the second half of pregnancy. The findings support the current hypothesis that teratogenic effects are likely mediated through disruptions in the renin-angiotensin axis and, therefore, not observed with such early exposures.
The study findings suggest that inadvertent exposure to ACE inhibitors/ARBs in the first trimester of pregnancy may not present significant risks for malformations in live births but may be associated with higher rates of spontaneous abortion. However, given the strong evidence for teratogenicity beyond the first trimester and the availability of other safer effective antihypertensives in pregnancy, it is imperative that women on such agents receive prompt attention in the early part of pregnancy so that their antihypertensive f pregnancy so that their antihypertensive
Source: Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2012, Article ID 658310 doi:10.1155/2012/658310
