Screening for pre‐eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation

Abstract

ObjectiveThere are four objectives in this study investigating the predictive performance of screening for delivery with preeclampsia (PE) and gestational hypertension (GH) at ≥37 weeks’ gestation. First, to examine the performance of maternal serum glycosylated fibronectin (GlyFn) at 35+0 to 36+6 weeks’ gestation in screening for delivery with PE and GH within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFLT‐1). Third, to compare the predictive performance for delivery with PE and GH with use of serum PlGF concentration, soluble sFLT‐1 / PlGF concentration ratio, and the competing risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11+0 to 13+6 vs 35+0 to 36+6 weeks’ gestation for delivery with PE and GH at ≥37 weeks’ gestation.MethodsThis was a case‐control study in which maternal serum GlyFn was measured in stored samples from a non‐intervention screening study in singleton pregnancies at 35+0 to 36+6 weeks’ gestation using a point‐of‐care device. We used samples from women who delivered at ≥37 weeks’ gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop either PE or GH. In all cases, MAP, UtA‐PI, PlGF and sFLT‐1 had been measured during the routine visit at 35+0 to 36+6 weeks. We used the samples from patients that had previously been examined at 11+0 to 13+6 weeks’ gestation. Levels of GlyFn were transformed to multiple of the expected median value (MoM) after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA‐PI, PlGF and sFLT‐1 were converted to MoMs. The competing risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient‐specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at 10% fixed false‐positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening.ResultsThe DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFLT‐1) was 83.7% (95% CI 70.3‐92.7%) for delivery with PE within 3 weeks of screening, it was 80.0% (70.8‐87.3%) for delivery with PE at any time after screening and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA‐PI and GlyFn was similar to that of the triple test, and they were both superior to screening by either low PlGF concentration (PE within 3 weeks: 65.3%, 50.4‐78.3%, PE at any time: 56%, 45.7‐65.9%) or high sFLT‐1 / PlGF concentration ratio (PE within 3 weeks: 73.5, 58.9‐85.1%, PE at any time 63%, 52.8‐72.4%). The predictive performance of screening at 35+0 to 36+6 weeks’ gestation for delivery with PE and GH at ≥37 weeks’ gestation was by far superior to screening at 11+0 to 13+6 weeks.ConclusionGlyFn, is a potentially useful biomarker in third‐trimester screening for term PE and term GH, but the results of this case‐control study need to be validated by prospective screening studies.This article is protected by copyright. All rights reserved.

Prediction using serum glycosylated fibronectin and angiogenic factors of superimposed pre‐eclampsia in women with chronic hypertension

“…A randomized trial is currently evaluating timed birth based on personalized risk of PE, a strategy that has the potential to decrease the rate of term PE by about 60% 9 . In two recent studies, we reported that glycosylated fibronectin (GlyFn) is a new biomarker that could potentially replace angiogenic markers in firstand third-trimester screening for preterm and term PE, respectively 10,11 .…”