Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Diav–Citrin, Orna; Shechtman, Svetlana; Halberstadt, Yehudit; Finkel-Pekarsky, Victoriya; Wajnberg, Rebecka; Arnon, Judy; Gianantonio, Elena Di; Clementi, Maurizio; Ornoy, Asher

doi:10.1016/j.reprotox.2011.02.008

Cited by 77 publications

(52 citation statements)

References 27 publications

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“…14). Although first-trimester effects of ACE inhibitors were suggested by one study, the majority of data supports a fetotoxic hazard only beyond the first trimester (30)(31)(32).…”

Section: Discussionmentioning

confidence: 95%

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

Padberg

Wacker

Meister

et al. 2014

Antimicrob Agents Chemother

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bFluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [OR adj ], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HR adj ], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [OR crude ], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HR adj , 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered.

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“…14). Although first-trimester effects of ACE inhibitors were suggested by one study, the majority of data supports a fetotoxic hazard only beyond the first trimester (30)(31)(32).…”

Section: Discussionmentioning

confidence: 95%

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

Padberg

Wacker

Meister

et al. 2014

Antimicrob Agents Chemother

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“…Six articles were excluded from the analysis because the listed cases were not described in detail [76][77][78][79][80][81] ; however, these reports were further explored for the description of the prevalence and general aspects of fetal RAS-blockade syndrome (see the online-only Data Supplement Expanded Results section with Figure S2) and the analysis of the prevalence of major congenital malformations.…”

Section: Search Resultsmentioning

confidence: 99%

“…76,[79][80][81] It is worthy of mention that the congenital malformations that occur following in utero exposure to a blocker of the RAS may result either directly from the drug as well as from the underlying maternal illness. It is well-recognized, for example, that pregestational diabetes mellitus is associated with a 2-to 3-fold increase in risk of malformations.…”

Section: Bullo Et Al Fetal Renin-angiotensin System Blockade Syndromementioning

confidence: 99%

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

Bullo

Tschumi²,

Bucher³

et al. 2012

Hypertension

293

152

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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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“…Recent studies suggest minimal teratogenicity of statins during pregnancy (36,37), although statins remain pregnancy category X drugs as labeled by the US FDA. ACEIs and angiotensin receptor blockers are associated with an increased risk of fetal birth defects (38), although risk with use in early pregnancy is comparable to that of other antihypertensive medications (39,40).…”

Section: Discussionmentioning

confidence: 99%

Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease

Cadnapaphornchai

George

McFann

et al. 2014

Clinical Journal of the American Society of Nephrology

153

101

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Background and objectives In autosomal dominant polycystic kidney disease (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because important manifestations of ADPKD may be evident in childhood, early intervention may have the largest effect on long-term outcome. Statins are known to slow progressive nephropathy in animal models of ADPKD. This randomized double-blind placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to assess the effect of pravastatin on height-corrected total kidney volume (HtTKV) and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and urine microalbumin excretion (UAE) in children and young adults with ADPKD.Designs, setting, participants, & measurements There were 110 pediatric participants with ADPKD and normal kidney function receiving lisinopril who were randomized to treatment with pravastatin or placebo for a 3-year period with evaluation at 0, 18, and 36 months. The primary outcome variable was a $20% change in HtTKV, LVMI, or UAE over the study period.Results Ninety-one participants completed the 3-year study (83%). Fewer participants receiving pravastatin achieved the primary endpoint compared with participants receiving placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47% versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and hypertension status over the 3-year period was significantly decreased with pravastatin (23%63% versus 31%63%; P=0.02).Conclusions Pravastatin is an effective agent to slow progression of structural kidney disease in children and young adults with ADPKD. These findings support a role for early intervention with pravastatin in this condition.

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Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Cited by 77 publications

References 27 publications

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

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

Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease

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