Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Department of Mathematics, Beuth Hochschule für Technik Berlin, Berlin, Germany.
Clin Res Cardiol. 2018 Aug;107(8):679-687. doi: 10.1007/s00392-018-1234-2. Epub 2018 Mar 24.
Ongoing discussion about the safety of renin-angiotensin inhibitors in the first trimester and limited data on pregnancy outcomes after exposure to angiotensin AT1 receptor blockers (ARBs).
Observational cohort study compares outcomes of 215 prospectively ascertained pregnancies with first trimester exposure to ARBs with 642 non-hypertensive pregnancies.
The rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in the comparison group (17/570, 3%), but not significantly increased (OR 1.9, 95% CI 0.7-4.9). There was no distinct pattern of anomalies among infants with birth defects. The risk of spontaneous abortions was not increased (HR 0.9, 95% CI 0.5-1.6), although the cumulative incidence was in the upper normal range (0.22, 95% CI 0.15-0.32). Higher rates of prematurity (OR 3.0; 95% CI 1.7-5.1) and a reduced birth weight after adjustment for sex and gestational age were observed. There was no evidence for an increased risk for major birth defects, spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB exposed hypertensive women to hypertensive women without ARB exposure during the first trimester.
Our study supports the hypothesis that ARBs are not major teratogens. Patients inadvertently exposed to ARBs during the early pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid ARBs. In selected cases, ARBs might be continued under careful monitoring of menstrual cycle and discontinued as soon as pregnancy is recognized.
关于血管紧张素转换酶抑制剂在妊娠早期的安全性仍存在争议，且关于接触血管紧张素 AT1 受体阻滞剂（ARB）后妊娠结局的数据有限。
本观察性队列研究比较了 215 例前瞻性确定的妊娠早期接触 ARB 的孕妇与 642 例非高血压孕妇的结局。
ARB 组（9/168，5.4%）的主要出生缺陷发生率高于对照组（17/570，3%），但差异无统计学意义（OR 1.9，95%CI 0.7-4.9）。有出生缺陷的婴儿中没有明显的畸形模式。自然流产的风险没有增加（HR 0.9，95%CI 0.5-1.6），尽管累积发生率处于正常上限（0.22，95%CI 0.15-0.32）。早产率较高（OR 3.0；95%CI 1.7-5.1），且在调整性别和胎龄后，出生体重降低。在敏感性分析中，将妊娠早期接触 ARB 的高血压女性与未接触 ARB 的高血压女性进行比较，未发现 ARB 暴露与主要出生缺陷、自然流产或早产风险增加有关。
我们的研究支持 ARB 不是主要致畸物的假设。意外在妊娠早期接触 ARB 的患者可以得到安抚。然而，计划妊娠的女性应避免使用 ARB。在某些情况下，应密切监测月经周期，并在确认妊娠后尽快停药。
