OP01.08: Value of adding angiogenic factors to ultrasound Doppler criteria in the definition of fetal growth restriction

To investigate the added value of maternal angiogenic factors to ultrasound and Doppler criteria currently used for the classification of small fetuses as low-risk small-for-gestational-age (SGA) or high-risk fetal growth restriction (FGR). Singleton pregnancies (N = 602) with a diagnosis of fetal smallness (defined as estimated fetal weight (EFW) and birthweight < 10th centile) and a gestational age at delivery ≥34 weeks' gestation were prospectively recruited. Ultrasound assessment of EFW and Doppler [uterine arteries pulsatility index (UtA-PI) and cerebroplacental ratio (CPR)] was performed at diagnosis. Biochemical analysis of PlGF and sFlt-1 in peripheral maternal venous blood was measured by ELISA. The primary outcome was APO defined as a composite of perinatal death or metabolic acidosis (umbilical artery pH < 7) or emergency Caesarean section for fetal distress or neonatal unit admission. The predictive value of EFW < 3rd centile, Doppler parameters (UtA-PI >95th centile and CPR < 5th centile) and sFlt-1/PlGF ratio >95th centile, alone or in combination was assessed by logistic regression. All parameters were independently associated with APO: EFW < 3rd centile [adjusted odds ratio 2.58 (1.67 – 4)], UtA-PI [aOR 1.92 (1.25 – 2.94)], CPR [aOR 2.35 (1.46 – 3.78)] and sFlt-1/PlGF [aOR 1.71 (1.09 – 2.69)]. The presence of pre-eclampsia was a significant modifier of these associations. The detection rate (DR) for APO of a combined model including EFW, UtA-PI and CPR was 86.8% with 62% false positives (FP). For a model including only sFlt1/PlGF the DR and FP were 39.8%% and 16.9% respectively whereas in combination with EFW the DR and FP were 81.3%% and 52.3% respectively. A model including all the parameters yielded a DR of 88.5% for a 64.5% of FP. Angiogenic factors as stand-alone criterion had a poor predictive value to identify high-risk FGR among late-onset small fetuses and it marginally improved the predictive value of currently used ultrasound-Doppler criteria.