Abstract / Summary
Abstract Introduction. Theoretically, factors predisposing to miscarriage may influence fetal development during a normal pregnancy, in particular, affect the development of the hemostasis system of the unborn child. However, the factors of hereditary predisposition to thrombophilia in children born to mothers with recurrent miscarriage have not been sufficiently studied. Objective. To identify the association of a number of hemostasis parameters (the D-dimer level and the level of INR) with the genotypes of genetic variants F5 c.1691G>A, ITGA2 с.807C>T and ITGB3 с.1565 T>C of the hemostasis system genes in pediatric patients born to mothers with recurrent miscarriage. Methods. We conducted a controlled observational study including 352 children born to mothers with a history of miscarriage, and 261 healthy children. D-dimer and INR were measured monthly for 12 months and averaged. Log-transformed D-dimer was analyzed using multivariable linear regression with interaction terms. Results. A strong association between F5 genotype and D-dimer levels was observed (both in the group, p<0.05). In the group of children born to mothers with miscarriage, D-dimer levels differed significantly across ITGA2 с.807C>T genotypes (p=0.0039); a genotype-dependent gradient (CC < CT < TT) of D-dimer levels was also identified. In multivariable regression showed the following results: F5 c.1691G>A remained highly significant (p<0.001), ITGA2 с.807C>T remained significant (p<0.001). Group status (Children vs Control) showed the strongest effect (p <0.001). Conclusion. Genetic variants in F5 and ITGA2 are independently associated with increased D-dimer levels, with a stronger effect observed in a high-risk pediatric cohort of children born to mothers with recurrent miscarriage.