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

Presented on behalf of the EVERREST Consortium.

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. This study identified and validated models containing ultrasound and/or maternal serum protein measurements at diagnosis to predict fetal or neonatal death and three secondary outcomes.

Methods: Women with singleton pregnancies (n = 142, estimated fetal weights [EFWs] <3rd centile, <600 g 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 linked to 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 of 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 (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery <28 + 0 weeks of gestation 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.