title: Angiotensin-II receptor 1 antagonist fetopathy--risk assessment, critical time period and vena cava thrombosis as a possible new feature.
abstract: OBJECTIVE
  Angiotensin-II receptor 1 antagonists (AT₁-antagonists) may cause severe and even lethal fetopathy in late pregnancy. However, exposure still occurs in spite of warnings in package leaflets. This study aimed to assess the risk of fetopathy, the sensitive time window, and possible new symptoms in prospective as well as retrospective cases with AT₁-antagonist treatment during the second or third trimester of pregnancy.
  
  
  METHODS
  Patients were enrolled by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy between 1999 and 2011 through risk consultation. Symptoms defined as indicative of AT₁-antagonist fetopathy were: oligo-/anhydramnios, renal insufficiency, lung hypoplasia, joint contractures, skull hypoplasia and fetal/neonatal death.
  
  
  RESULTS
  In 5/29 (17%) prospectively enrolled cases with AT₁-antagonist exposure beyond the first trimester oligo-/anhydramnios was diagnosed. Two infants showed additional symptoms of fetopathy. The risk is more than 30% if treatment continues beyond the 20th week of pregnancy. Oligo-/anhydramnios was reversible after AT₁-antagonist withdrawal. Among 16 retrospective case reports, three infants presented with a thrombosis of the inferior vena cava in the vicinity of the renal veins. Four out of 13 live births did not survive.
  
  
  CONCLUSIONS
  Our survey suggests that the risk increases with duration of AT₁-antagonist treatment into late pregnancy and oligo-/anhydramnios may be reversible after AT₁-antagonist discontinuation. Thrombosis of inferior vena cava may be a new feature of AT₁-antagonist fetopathy. AT₁-antagonist medication during pregnancy constitutes a considerable risk and must be discontinued immediately. In case of indicative diagnostic findings in either the fetus or newborn, previous maternal AT₁-antagonist exposure should be considered.
authors: Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, 14050 Berlin, Germany.
authors: Marc
authors: M
authors: Oppermann
authors: Stephanie
authors: S
authors: Padberg
authors: Angela
authors: A
authors: Kayser
authors: Corinna
authors: C
authors: Weber-Schoendorfer
authors: Christof
authors: C
authors: Schaefer
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000175:diagnosis / Q000209:etiology*; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D005260:Female; D005313:Fetal Death; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008423:Maternal Age; D016104:Oligohydramnios / Q000139:chemically induced; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced*; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000187:drug effects* / Q000473:pathology; D020246:Venous Thrombosis / Q000139:chemically induced* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers