Abstract
Pregnancy results in alterations in coagulation processes, which may increase the
risk of thrombosis. Inherited thrombophilia mutations may further increase this risk,
possibly through alterations in the placenta, which may result in pregnancy complications
such as poor fetal growth. The purpose of our study is to evaluate the association
of fetal growth, approximated by birth weight for gestational age percentile, with
genetic markers of thrombophilia and placental characteristics related to vascular
malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's
population-based case–control study conducted in 2006–2008. Study recruitment occurred
in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah.
The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation
with a complete placental examination and successful testing for ≥1 thrombophilia
marker (858 mothers, 902 infants). Data were weighted to account for oversampling,
differential consent, and availability of placental examination. We evaluated five
thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate
reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal
blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers
separately using linear regression. Maternal factor V Leiden mutation was associated
with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval:
−25.50, −0.82). Adjustment for placental abnormalities related to vascular malperfusion
did not affect the observed association. No other maternal or fetal thrombophilia
markers were significantly associated with birth weight percentile. Maternal factor
V Leiden may be associated with fetal growth independent of placental characteristics.
Keywords
pregnancy - inherited thrombophilias - perinatal hemostasis
