Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing‐risks model
Authors: Schiattarella A. , Magee L. A. , Wright A. , Syngelaki A. , Akolekar R. , von Dadelszen P. , Nicolaides K. H. 
Published: June 2023

ABSTRACTObjectiveTo compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre‐eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio, or the competing‐risks model, which combines maternal risk factors with biomarkers to estimate patient‐specific risk.MethodsThis was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt‐1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt‐1/PlGF ratio (> 90th percentile); or (iii) the competing‐risks model, in which maternal factors were combined with multiples of the median values of PlGF (‘single test’), PlGF and sFlt‐1 (‘double test’) or PlGF, sFlt‐1 and MAP (‘triple test’). Risk cut‐offs corresponded to a screen‐positive rate of 10%. DRs were compared between tests.ResultsOf 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen‐positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt‐1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt‐1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7–23.0%) and 12.4% (9.7–15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9–26.8%) and 12.9% (7.7–17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4–21.6%) and 5.4% (0.0–10.8%), respectively). The double test was superior to the sFlt‐1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment.ConclusionAt 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing‐risks model triple test is superior to that of PlGF alone or the sFlt‐1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.