Warfarin is a coumarin anticoagulant and vitamin K antagonist which acts by inhibiting clotting factors II, VII, IX and X. It is indicated for: the prevention of systemic embolism in patients with rheumatic heart disease and atrial fibrillation, prophylaxis after insertion of mechanical heart valves, prophylaxis and treatment of venous thrombosis and pulmonary embolism, and treatment of transient cerebral ischaemic attacks.
Warfarin exposure in the first trimester can lead to an embryopathy known as fetal warfarin syndrome (FWS), characterised by nasal hypoplasia and skeletal abnormalities, including short limbs and digits, and stippled epiphyses. The critical risk period for FWS has not been definitively confirmed but is thought likely to span gestational weeks 6 to 12. The likelihood of warfarin embryopathy following exposure during this period has been proposed to be as high as 30%, although more recent studies suggest a risk of 6-10%. There is some evidence that the risk of FWS may be dose-dependent, with doses of >5mg carrying a higher risk, although doses lower than this are not without risk.
Warfarin exposure that extends beyond or commences after the first trimester of pregnancy has been associated with CNS defects and eye anomalies. Second and third trimester exposure confers a risk of fetal, placental, or neonatal haemorrhage.
Developmental delay has been observed in children with in utero exposure to warfarin, but when reported was mainly in those with FWS.
Use of warfarin in pregnancy may be associated with an increased incidence of miscarriage; this has also been reported following use of other anticoagulants such as heparin. Other pregnancy outcomes have not been adequately studied to allow an accurate assessment of risk.
Warfarin exposure in pregnancy should be avoided, if possible, by changing to a non-teratogenic anticoagulant, usually a low molecular weight heparin (LMWH), before pregnancy or as soon as possible after pregnancy is suspected. In some patients with mechanical heart valves the continued use of warfarin may need to be considered since anticoagulation with LMWH may be less effective. All patients with mechanical valves should be referred for pre-conception counselling and contraceptive advice. If they become pregnant, immediate referral to a tertiary maternal-cardiology centre is advised.
Detailed ultrasound scans should be considered to screen for structural anomalies associated with FWS where exposure has occurred during the first trimester. Women with ongoing warfarin use in pregnancy will usually be offered additional monitoring of fetal growth and wellbeing.
Other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.