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] <3rd 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.

Epigenetic scores indicate differences in the proteome of preterm infants

“…As well as having specific immunoregulatory roles, in the neonatal setting or relevant animal models, these proteins are associated with several comorbidities and developmental consequences of preterm birth. These include lung development and disease such as BPD [55][56][57][58][59][60][61][62][63][64][65][66][67], in utero and postnatal growth failure [68][69][70][71], HCA [7,72,73], patent ductus arteriosus [74][75][76][77], retinopathy of prematurity [78][79][80][81][82], NEC [83][84][85], hyperglycaemia [86], sepsis [85,[87][88][89][90], brain injury [32,[91][92][93][94], and neurodevelopmental outcomes [95][96][97][98]…”