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Pregnancy
Further information: Anticoagulation in pregnancy
Warfarin is contraindicated in pregnancy, as it passes through the placental barrier and may cause bleeding in the fetus; warfarin use during pregnancy is commonly associated with spontaneous abortion, stillbirth, neonatal death, and preterm birth.[17] Coumarins (such as warfarin) are also teratogens, that is, they cause birth defects; the incidence of birth defects in infants exposed to warfarin in utero appears to be around 5%, although higher figures (up to 30%) have been reported in some studies.[18] Depending on when exposure occurs during pregnancy, two distinct combinations of congenital abnormalities can arise.[17]
When warfarin (or another 4-hydroxycoumarin derivative) is given during the first trimester—particularly between the sixth and ninth weeks of pregnancy—a constellation of birth defects known variously as fetal warfarin syndrome (FWS), warfarin embryopathy, or coumarin embryopathy can occur. FWS is characterized mainly by skeletal abnormalities, which include nasal hypoplasia, a depressed or narrowed nasal bridge, scoliosis, and calcifications in the vertebral column, femur, and heel bone which show a peculiar stippled appearance on X-rays. Limb abnormalities, such as brachydactyly (unusually short fingers and toes) or underdeveloped extremities, can also occur.[17][18] Common non-skeletal features of FWS include low birth weight and developmental disabilities.[17][18]
Warfarin administration in the second and third trimesters is much less commonly associated with birth defects, and when they do occur, are considerably different from fetal warfarin syndrome. The most common congenital abnormalities associated with warfarin use in late pregnancy are central nervous system disorders, including spasticity and seizures, and eye defects.[17][18] Because of such later pregnancy birth defects, anticoagulation with warfarin poses a problem in pregnant women requiring warfarin for vital indications, such as stroke prevention in those with artificial heart valves.
Usually, warfarin is avoided in the first trimester, and a low molecular weight heparin such as enoxaparin is substituted. With heparin, risk of maternal hemorrhage and other complications is still increased, but heparins do not cross the placental barrier and therefore do not cause birth defects.[18] Various solutions exist for the time around delivery.
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