Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves.
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.
Vitale
N
N
Department of Cardiac Surgery, Medical School, Monaldi Hospital, Second University of Naples, Italy. Nicola.Vitale@ncl.ac.uk
De Feo
M
M
De Santo
L S
LS
Pollice
A
A
Tedesco
N
N
Cotrufo
M
M
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*
D000925:Anticoagulants; D014859:Warfarin