Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study

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.

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.

Retrospective cohort study in a geographically-defined area.

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.

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).

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.