The effect of maternal soluble FMS-like tyrosine kinase 1 during pregnancy on risk of preterm delivery

Objective: Soluble fms-like tyrosine kinase 1 (sFlt1) is an antiangiogenic protein that is associated with a number of disorders of placental angiogenesis. It has been hypothesized that disruption of placental angiogenesis may contribute to the pathophysiology of preterm delivery (PTD). However, the relationship of PTD risk to variation in sFlt1 levels is not well known. We investigate the relationship between longitudinal variation in maternal serum concentrations of sFlt1 and risk of PTD. Methods: Data were collected in a longitudinal cohort study involving 278 pregnant women. Maternal serum sFlt1 concentrations were measured at 610, 1014, 1620, 2226, and 3236 weeks gestation. Data analyses used longitudinal regression models using repeated measures that allow robust inferences from our modest sample size. The outcome was birth prior to 37 weeks gestation. Results: sFlt1 concentrations were higher in first trimester for preterm compared to term deliveries. This relationship reversed in second trimester because sFlt1 concentrations increased more rapidly across gestation for term deliveries. In Cox proportional hazards analyses, a 2ng higher sFlt1 concentration across gestation was associated with a hazard ratio of 1.3 (95% CI: 1.1, 1.5) for PTD suggesting the importance of levels in early pregnancy. Conclusion: Elevated maternal serum sFlt1 concentration during pregnancy is associated with increased risk of PTD.