Background: The factor V Leiden (FVL) mutation is the most common cause of inherited thrombophilia in Caucasian populations, and women with this variant allele are at increased risk for pregnancy complications.
Aim: To examine whether the FVL allele is associated with pregnancy complications and adverse outcomes in a population-based study, and to identify potential factors that interact with the FVL genotype.
Design: Retrospective cohort study in a geographically-defined area.
Methods: Polymorphisms of factor V 1691G-->A, methylenetetrahydrofolate reductase (MTHFR) 677C --> T and 1298A --> C and plasma levels of total homocysteine, folate and vitamin B(12) were determined in blood samples collected in 1992-1993 from 5874 women aged 40-42 years, and linked with 14 474 pregnancies in the same women, recorded in the Medical Birth Registry of Norway, 1967-1996.
Results: The allelic frequency of FVL was 3.7% (6.9% heterozygotes, 0.3% homozygotes). Maternal FVL mutation was associated with significantly higher risks of pre-eclampsia (OR 1.63, 95%CI 1.15-2.30), pre-eclampsia at <37 weeks (OR 2.76, 1.34-5.70), low birth weight (OR 1.34, 95%CI 1.03-1.74) and stillbirth (OR 2.20, 95%CI 1.45-3.36). The presence of a variant allele for the 677C --> T MTHFR polymorphism strengthened the association between FVL and stillbirth (OR 3.34, 95%CI 1.95-5.73) (p(interaction) = 0.034).
Discussion: FVL mutation is a significant risk factor for pregnancy complications and adverse outcomes, and MTHFR 677CT/TT genotype can further enhance the risk of stillbirth.