Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves

Abstract

Objectives: 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.