Pregnancy Outcome Following Exposure to Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Antagonists

Abstract

Abstract-The objective was to analyze the outcome following prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor antagonists (ARBs). For this purpose, a systematic review of published case reports and case series dealing with intrauterine exposure to ACE-Is or to ARBs using Medline as the source of data was performed. The publications retained for analysis included patients who were described individually, revealing, at minimum, the gestational age, substance used, period of medication intake, and the outcome. In total, 72 reports were included; 37 articles (118 well-documented cases) described the prenatal exposure to ACE-Is; and 35 articles (68 cases) described the prenatal exposure to ARBs. Overall, 52% of the newborns exposed to ACE-Is and 13% of the newborns exposed to ARBs did not exhibit any complications (PϽ0.0001). Neonatal complications were more frequent following exposure to ARBs and included renal failure, oligohydramnios, death, arterial hypotension, intrauterine growth retardation, respiratory distress syndrome, pulmonary hypoplasia, hypocalvaria, limb defects, persistent patent ductus arteriosus, or cerebral complications. The long-term outcome is described as positive in only 50% of the exposed children. Fetopathy caused by exposure to ACE-Is or ARBs has relevant neonatal and long-term complications. The outcome is poorer following exposure to ARBs. We propose the term "fetal renin-angiotensin system blockade syndrome" to describe the related clinical findings. Thirty years after the first description of ACE-I fetopathy, relevant complications are, at present, regularly described, indicating that the awareness of the deleterious effect of prenatal exposure to drugs inhibiting the renin-angiotensin system should be improved. A n undamaged renin-angiotensin system (RAS) is a prerequisite for normal prenatal renal development. Loss of function mutations in the genes encoding the RAS present with a disturbed renal development, characterized by reduced fetal diuresis, leading to oligohydramnios and, occasionally, skull-ossification defects. At birth, blood pressure is low, and death occurs in most cases.1 This clinical scenario resembles the findings, first reported by Guignard et al 2 and Duminy et al 3 in 1981, in infants exposed during pregnancy to drugs that block the RAS. This condition, which occurs following maternal treatment with either angiotensinconverting enzyme inhibitors (ACE-Is) or angiotensin receptor antagonists (ARBs), is usually termed fetal reninangiotensin system blockade syndrome (fetal RAS-blockade syndrome). Some data also indicate a possible association between the use of these drugs during the first trimester of pregnancy and congenital malformations.Because the adverse effects of drugs that block the RAS in the unborn child have been described only in single-case reports or in small case series, we performed a formal systematic analysis of the literature that addresses the intrauterine exposure to ACE-Is or ARBs. Our purposes in con...

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