The value of angiogenetic biomarkers in the detection of early onset fetal growth restriction.

ABSTRACT

OBJECTIVE: The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors. STUDY DESIGN: This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age. RESULTS: 72 pregnancies with SGA were first evaluated at median (IQR) of 28+5 (26+2 -31+3) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR 0.07-0.36 vs 0.32, 95 % IQR 0.20-0.53, p = 0.008) and 0.26, 95 % CI 0.16-0.55 vs 0.43, 95 % IQR 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR 1.80-7.30 vs 1.74, 95 % IQR1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR 0.27-3.07 vs 0.17, 95 % IQR 0.08-0.43, p = 0.022). CONCLUSION: These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR.