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Familial defects and polymorphisms of clotting cascade proteins protein S, protein C, factor V Leiden G1691A and factor II G20210A are linked with increased risk of thromboembolism which is better known as inherited thrombophilia. Thrombophilia causes deep venous thrombosis, pulmonary embolism and is strongly associated with poor pregnancy outcomes. Pathophysiology of these outcomes is thought to involve thrombosis in uteroplacental blood flow hence, anticoagulation therapy can potentially improve obstetric outcome in females with thrombophilias. To date, there is limited data from this region on the role of these genetic abnormalities causing adverse pregnancy outcomes.

Determine the association of factor V Leiden G1691A and prothrombin gene G20210A mutation with adverse pregnancy outcomes.

It was a case control study, conducted at clinical laboratory, section of haematology, and PCR-RFLP technique is used at multi-disciplinary laboratory, Aga Khan University Hospital. Females with adverse pregnancy outcomes who came to obstetrical clinic were included in the study as cases.  Adverse pregnancy outcomes included recurrent pregnancy loss (defined as > 2 first trimester miscarriages or one or more second trimester miscarriage), severe pre-eclampsia, placental abruption, intrauterine growth restriction and still birth.

Control samples are selected from females with ≥ 2 consecutive normal pregnancies. Calculated sample size is 172 which comprise of 86 cases and 86 controls.

Overall mean age of all subjects was 28.5 years (±4.9). Mean age of cases was 29.3 (±5.17) years and of controls was 27.6 years (±4.5). 73 (84.8%) cases had recurrent pregnancy loss, 12 (13.9%) had pre-eclampsia, 8 (9.3%) had IUGR while placental abruption and still birth was present in 2 (2.3%) cases each. 10 (11.6%) cases had more than one adverse pregnancy outcomes. 19 (22.09%) cases had > 4 pregnancy losses. Among cases, 40 (46.5%) females had previous live births and 9 (10.4%) were pregnant at the time of sample collection.

Two cases with recurrent pregnancy loss (p=0.155 OR=0.49) showed heterozygous mutation of factor V Leiden G1691A and while no mutation identified in the control arm. Heterozygous prothrombin gene mutation was identified in one case with recurrent pregnancy loss (p= 0.316 OR=0.497) while none of the control exhibited this mutation.

This is a small sample sized study which does not support a significant association between inherited thrombophilia mutations and adverse pregnancy outcomes. The apparent lack of association may be reconciled by the low numbers of subjects recruited.