title: Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in women at suspected risk for thromboembolic events: a case series from the German Embryotox Pharmacovigilance Centre.
abstract: BACKGROUND
  New oral anticoagulants are increasingly used in women of childbearing age, but apart from one case report there is no published experience with rivaroxaban exposure during pregnancy.
  
  
  METHODS
  From October 2008 to December 2014, the German Embryotox Pharmacovigilance Centre identified 63 exposed pregnancies among 94 requests concerning rivaroxaban use during childbearing age. Follow-up included paediatric checks until 6 weeks after birth.
  
  
  RESULTS
  All pregnancies with completed follow-up were exposed at least during the first trimester. Treatment indications included venous thromboembolism, knee surgery, and atrial fibrillation. 37 pregnancies were prospectively ascertained and resulted in six spontaneous abortions, eight elective terminations of pregnancy, and 23 live births. All women had discontinued rivaroxaban after recognition of pregnancy, mostly in the first trimester, but in one woman treatment continued until gestational week 26. There was one major malformation (conotruncal cardiac defect) among the 37 prospectively ascertained pregnancies in a woman with complex medication and a previous foetus with cardiac malformation without exposure to rivaroxaban. Only one case of bleeding concerning a retrospective report of surgery for missed abortion was observed in our case series.
  
  
  CONCLUSIONS
  Our results might give reassurance to those women, who were inadvertently exposed to rivaroxaban in early pregnancy. However, our limited cohort size does not allow ruling out an increased malformation risk and does not support the use of rivaroxaban during pregnancy. In all cases of (inadvertent) rivaroxaban exposure during 1st trimester, anticoagulation regimen should be reconsidered and a detailed ultrasound assessment recommended to confirm normal foetal development.
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. maria.hoeltzenbein@charite.de.|Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. maria.hoeltzenbein@charite.de.
authors.forename: M
authors.initials: M
authors.lastname: Hoeltzenbein
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Beck
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Meixner
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D060735:Pharmacovigilance; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000453:epidemiology; D011256:Pregnancy Outcome; D011446:Prospective Studies; D012189:Retrospective Studies; D012306:Risk; D000069552:Rivaroxaban / Q000008:administration & dosage* / Q000009:adverse effects; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D000069552:Rivaroxaban
keywords: New oral anticoagulants; Non-vitamin K antagonist oral anticoagulants; Pregnancy; Rivaroxaban; Venous thromboembolism