Increased risk for fetal loss in carriers of the factor V Leiden mutation

An increased risk for fetal loss caused by placental thrombosis is probable in carriers of the factor V Leiden mutation but has not been demonstrated consistently in previous studies.

To determine the overall risk for fetal loss and the separate risks for miscarriage and stillbirth in carriers of the factor V Leiden mutation.

Retrospective cohort study.

Three university hospitals.

228 carriers of the factor V Leiden mutation (77 propositi, 151 relatives) and 121 noncarrier relatives (controls). All participants had been pregnant at least once.

Risks for fetal loss, miscarriage (defined as fetal loss within 20 weeks of gestation), and stillbirth (defined as fetal loss after >20 weeks of gestation) in women and in pregnancies were estimated and compared in carriers and noncarriers. Adjusted odds ratios were calculated by using multiple regression analysis. A random-effects model was used for comparisons of pregnancies.

Fetal loss occurred in 31.6% of carriers and 22.3% of noncarriers, miscarriage occurred in 29.4% of carriers and 17.4% of noncarriers, and stillbirth occurred in 5.7% of carriers and 5.0% of noncarriers. Fetal loss recurred in 10.1% of carriers and 4.1% of noncarriers (odds ratio, 2.60 [95% CI, 0.96 to 7.03]). Adjusted odds ratios were 2.12 (CI, 1.35 to 3.33) for fetal loss, 2.08 (CI, 1.33 to 3.25) for miscarriage, and 1.60 (CI, 0.58 to 4.43) for still-birth when pregnancies in carriers and noncarriers were compared. Homozygous carriers had a greater risk for fetal loss (odds ratio, 2.01 [CI, 0.94 to 4.32]) and stillbirth (odds ratio, 4.85 [CI, 0.82 to 25.58]) than heterozygous carriers.

Carriers of the factor V Leiden mutation have a greater risk for fetal loss (particularly miscarriage) than noncarriers. These data further suggest a greater risk for recurrence of fetal loss in carriers than in noncarriers and a greater risk for fetal loss and stillbirth in homozygous carriers than in heterozygous carriers.