Ultrasound and biochemical predictors of pregnancy outcome at diagnosis of early-onset fetal growth restriction

Abstract Background Severe early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, preventing accurate patient counselling. We investigated the use of maternal serum protein and ultrasound measures at diagnosis to predict fetal or neonatal death and three secondary outcomes: fetal death or delivery ≤28+0 weeks; development of abnormal umbilical artery Doppler velocimetry; slow fetal growth. Methods Women with singleton pregnancies (n=142, estimated fetal weights EFWs <3 rd centile, <600g 20+0-26+6 weeks of gestation, no known chromosomal, genetic or major structural abnormalities), were recruited from four European centres. Maternal serum from the discovery set (n=63) was analysed for seven proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease and five proteins identified through pooled liquid chromatography tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n=60), with final models calculated from combined data. Results The most discriminative model for fetal or neonatal death included EFW z-score (Hadlock 3 formula/Marsal chart), gestational age and umbilical artery Doppler category (AUC 0.91, 95%CI 0.86-0.97) but was less well calibrated than the model containing only EFW z-score (Hadlock3/Marsal). The most discriminative model for fetal death or delivery ≤28+0 weeks included maternal serum placental growth factor (PlGF) concentration and umbilical artery Doppler category (AUC 0.89, 95%CI 0.83-0.94). Conclusion Ultrasound measurements and maternal serum PlGF concentration at diagnosis of severe early-onset FGR predict pregnancy outcomes of importance to patients and clinicians. Trial registration ClinicalTrials.gov NCT02097667 Funding European Union, Rosetrees Trust, Mitchell Charitable Trust.