The influence of specific mutations in the AT gene (SERPINC1) on the type of pregnancy related complications

Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P=0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant.