title: Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves.
abstract: OBJECTIVE
  The purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent.
  
  
  BACKGROUND
  Gravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients.
  
  
  METHODS
  Forty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage < or = 5 mg and > 5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently.
  
  
  RESULTS
  A total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were > 5 mg had 22 fetal complications, whereas those taking a dose < or = 5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; p < 0.7316).
  
  
  CONCLUSIONS
  There is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation.
authors.affiliation: Department of Cardiac Surgery, Medical School, Monaldi Hospital, Second University of Naples, Italy. Nicola.Vitale@ncl.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Vitale
authors.forename: M
authors.initials: M
authors.lastname: De Feo
authors.forename: L S
authors.initials: LS
authors.lastname: De Santo
authors.forename: A
authors.initials: A
authors.lastname: Pollice
authors.forename: N
authors.initials: N
authors.lastname: Tedesco
authors.forename: M
authors.initials: M
authors.lastname: Cotrufo
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death / Q000209:etiology; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007231:Infant, Newborn; D019934:International Normalized Ratio; D008297:Male; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D011475:Prosthesis Failure; D013927:Thrombosis / Q000188:drug therapy; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin