A literature search for all case reports and available literature was conducted in PubMed, Medline, and EMBASE up to December 2016 using medical subject heading terms \"mechanical prosthetic valves,\" \"pregnancy,\" \"oral anticoagulants,\" \"warfarin,\" \"coumarins,\" \"heparin, low-molecular-weight,\" and \"thromboembolism.\" To be included, warfarin had to be administered anytime between 6 and 12 weeks of gestation with the dose being specified. The Newcastle-Ottawa Scale was used to assess quality of the cohort data.
The woman in the studied case received the highest reported warfarin doses throughout pregnancy (14.5-16.5 mg daily) and delivered a baby with no evidence of teratogenicity to the current age of 5 years. The study identified 23 case reports, with all demonstrating warfarin teratogenicity regardless of high-dose (n = 12) or low-dose (n = 11) warfarin. Twelve cohort studies identified a warfarin teratogenicity rate of 5.0%, with rates of 2.4% and 10.5% with low- and high-dose warfarin, respectively. Risk of bias was moderate (median Newcastle-Ottawa Scale score of 6) for all of the cohort studies.
Although a lower prevalence of warfarin-induced teratogenicity is reported with low-dose warfarin, a safe \"cut-off\" dose is misleading. Teratogenic risk with warfarin is unpredictable, mandating individual decisions regardless of the dose.