Maternal thrombophilia and intrauterine growth restriction: A review of current evidence and clinical implications

Abstract

Intrauterine growth restriction (IUGR) is a significant contributor to perinatal illness and death, arising from a variety of complex and multifactorial causes. Increasing evidence suggests that maternal thrombophilia, particularly deficiencies in natural anticoagulants such as Protein C, Protein S, and Antithrombin III, is a key factor in placental dysfunction and impaired fetal growth. These effects are thought to occur via placental thrombosis, impaired spiral artery remodelling, and reduced placental perfusion, which can compromise fetal growth. This systematic review, covering studies published between 1963 and 2025 and compiles and evaluates existing research on the association between thrombophilic conditions and IUGR. Although several studies have reported an increased prevalence of thrombophilia markers in pregnancies affected by IUGR, the overall evidence is inconclusive. Variability in study design, patient populations, and diagnostic definitions of both thrombophilia and IUGR contributes to conflicting findings and hinders firm conclusions regarding their role in diagnosis or intervention. Additionally, the review explores the role of anticoagulant therapies, including low molecular weight heparin, in enhancing pregnancy outcomes for women with these conditions. However, the evidence is limited by small study sizes, design constraints, and regional biases, underscoring the necessity for larger, multicenter investigations. Current findings highlight the importance of further research into the contribution of thrombophilia in IUGR. While thrombophilia screening may hold potential for risk stratification in selected high-risk populations, current evidence does not support universal screening in routine prenatal care. Larger, multicentred studies are needed before screening strategies can be formally recommended.