High-Versus Low-Dose Warfarin-Related Teratogenicity: A Case Report and Systematic Review

Objective: The optimal anticoagulant therapy during pregnancy in women with mechanical heart valves remains controversial. This study highlights a case of high-dose warfarin ingestion throughout pregnancy and performed a systematic review to assess rates of teratogenicity with high versus low warfarin dosing (<= 5 mg daily). Methods: 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. Results: 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. Conclusion: 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.