OC02.03: *Correlation of angiogenic factors PlGF and sFlt‐1 with severity stages of fetal growth restriction

The current management of small fetuses relies on a stage-based approach according to ultrasound assessment of estimated fetal weight (EFW) and Doppler. The aim of this study was to investigate the profile of maternal angiogenic factors across the different clinical stages of small for gestational age (SGA) and fetal growth restriction (FGR). A total of 1028 singleton pregnancies were prospectively recruited including pregnancies with small fetuses (defined as EFW and birthweight <10th centile, N = 604) and uncomplicated pregnancies (N = 424). Ultrasound assessment of EFW and Doppler (uterine, umbilical, middle cerebral arteries and ductus venosus pulsatility index) was performed at diagnosis and monitored regularly until delivery. Small fetuses were classified as SGA or FGR (and within FGR into stage I, II or III+). Biochemical analysis of PlGF and sFlt-1 in peripheral maternal venous blood was performed by ELISA. Linear trend of proportions was tested using Mantel–Haenszel Chi2 test. The proportion of pregnancies with PlGF <5th centile was 8% in controls, 9.4% in SGA (N = 192), 31.6% in FGR stage I (N = 380), 37.5% in FGR stage II (N = 16) and 50% in FGR stage III+ (N = 16), p = 0.0001); sFlt-1>95th centile (8.3% in controls, 6.8% in SGA, 16.8% in FGR stage I, 18.8% in FGR stage II and 43.8% in FGR stage III+, p = 0.0001); and, sFlt-1/PlGF ratio >95th centile (12.7% in controls, 7.8% in SGA, 30.8% in FGR stage I, 43.8% in FGR stage II and 62.5% in FGR stage III+, p = 0.0001). In the whole population of small fetuses, sFlt-1/PlGF ratio >95th centile was 60.4% in cases with and 17.4% without pre-eclampsia. The linear trend was significant for all parameters in FGR with and without pre-eclampsia except for sFlt-1>95th centile in normotensive FGR. The proportion of abnormal maternal levels of angiogenic factors increased across the stages of severity of FGR. In most cases elevated angiogenic factors indicated the coexistence of pre-eclampsia. The association with fetal Doppler deterioration in normotensive FGR was weak.