Angiotensin II Receptor Blockers in Pregnancy: A Case Report and Systematic Review of the Literature

Sungkyunkwan University, Sŏul, Seoul, South Korea
Hypertension in Pregnancy (Impact Factor: 1.41). 02/2007; 26(1):51-66. DOI: 10.1080/10641950601147937
Source: PubMed


To describe the case of a woman exposed to angiotensin-II receptor blockers (ARBs) in the preconceptional period and to systematically review the literature on the safety of these drugs when used by pregnant women.
The case was identified at the Korean Motherisk Program (Seoul). For the systematic review, we searched the PubMed for case reports, case series, and post-marketing surveys.
A hypertensive woman was exposed to irbesartan prior to conception. The embryo had delayed development of upper and lower extremities and decreased digital groove. A karyotype identified a 45,XO Turner syndrome. The patient had a spontaneous abortion. Including the case reported here, 64 published cases were identified in total; 57.8% had favorable and 42.2% had unfavorable outcomes. Duration of treatment during pregnancy among women who had adverse fetal outcomes was 26.3 +/- 10.5 weeks (mean +/- SD), compared with 17.3 +/- 11.6 weeks in those who had favorable outcomes (p = 0.04).
Exposure to ARBs for a period longer than the first trimester of pregnancy appears to be associated with a high risk for adverse fetal outcomes.

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    • "For instance, it is involved in the maturation and growth of the fetal and postnatal heart and kidney [6]–[9]. Indeed, the use of ARBs during pregnancy is associated with an increased probability for cardiac and renal dysplasia in newborn infants, thereby indicating that AT1 receptor blockade and/or unopposed endogenous stimulation of the AT2 receptor, the predominant angiotensin II receptor subtype in the fetal and early postnatal organism, may negatively affect cardiac as well as renal maturation and growth [10], [11]. In this regard, the role of the AT2 receptor in postnatal development of the heart is rather unclear and has not been examined in detail so far. "
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    ABSTRACT: Background The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. Methodology/Principal Findings Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of α-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca2+ transient in response to isoprenaline when stimulated concomitantly with angiotensin II. Conclusion The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.
    Full-text · Article · Oct 2012 · PLoS ONE
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    • "Other abnormalities reported in association with ARBs include pulmonary hypoplasia, skull-bone hypoplasia, broadly spaced calvaria, craniofacial dysmorphia, limb deformations, and joint contractures [1,4–9]. In contrast, exposure to ARBs in the first trimester of pregnancy has been associated with low risk of fetopathy [2] [4] [7] [9]. "
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    ABSTRACT: To present cases exhibiting possible effects of angiotensin II receptor blockers (ARBs) received in pregnancy on the fetus. Retrospective analysis included women who delivered between 2002 and 2006 at Department of Obstetrics and Gynaecology Ljubljana. Antihypertensive medications were prescribed to 346 of the 26,735 women. ARBs were given in only five pregnancies: two women received losartan, and three irbesartan. The therapy was stopped between 5 and 23 weeks of gestation. Two women delivered healthy babies at term; another term baby had one additional finger and toe. Other two pregnancies were complicated with oligohydramnios and ended in preterm delivery. One preterm infant had transient abnormal renal function tests. Women should be informed that ARB-antihypertensive therapy must be replaced/stopped before planning their pregnancy or at least as soon as the pregnancy is confirmed. Fetal morphology scan and monitoring of amniotic fluid volume should be obligatory, if ARBs are prescribed accidentally.
    Full-text · Article · Aug 2009 · Reproductive Toxicology
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    ABSTRACT: More than 19 million Americans are affected by type 2 diabetes mellitus, which is undiagnosed in one third of these persons. In addition, it is estimated that more than 54 million adults have prediabetes. Debate continues over the benefits and harms of screening and then treating adults who have asymptomatic diabetes or prediabetes. To update the 2003 U.S. Preventive Services Task Force review on the evidence for potential benefits and harms of screening adults for type 2 diabetes and prediabetes in primary care settings. MEDLINE and the Cochrane Library for relevant studies and systematic reviews published in English between March 2001 and July 2007. Trials and observational studies that directly addressed the effectiveness and adverse effects of screening interventions were included. Randomized, controlled trials were used to assess the effectiveness of diabetes and prediabetes treatments. For diabetes interventions, trials of patients with disease for 1 year or less were included, as well as trials comparing outcomes among diabetic and nondiabetic patients. Relevant data were abstracted in duplicate into a standardized template. Data were synthesized in a qualitative manner, and a random-effects meta-analysis of the effects of interventions in prediabetes on the incidence of diabetes was performed. Most of the data on diabetes treatment were not from primary trial data but from subgroup analyses. Participants in intensive lifestyle interventions for prediabetes may not be representative of general prediabetic populations. Direct evidence is lacking on the health benefits of detecting type 2 diabetes by either targeted or mass screening, and indirect evidence also fails to demonstrate health benefits for screening general populations. Persons with hypertension probably benefit from screening, because blood pressure targets for persons with diabetes are lower than those for persons without diabetes. Intensive lifestyle and pharmacotherapeutic interventions reduce the progression of prediabetes to diabetes, but few data examine the effect of these interventions on long-term health outcomes.
    Preview · Article · Jun 2008 · Annals of internal medicine
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