Screening for pre‐eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation
Authors: Sokratous N. , Wright A. , Syngelaki A. , Kakouri E. , Laich A. , Nicolaides K. H. 
Published: September 2023

Objectives

First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre‐eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with 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 delivery with GH by serum PlGF concentration, 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 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation.

Methods

This 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 PE or GH. In all cases, MAP, UtA‐PI, PlGF and sFlt‐1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values 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 MoM. 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 a 10% fixed false‐positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening.

Results

The 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 and 80.0% (95% CI, 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 low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4–78.3%); PE at any time: DR, 56.0% (95% CI, 45.7–65.9%)) or high sFlt‐1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9–85.1%); PE at any time: DR, 63.0% (95% CI, 52.8–72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks.

Conclusion

GlyFn is a potentially useful biomarker in third‐trimester screening for term PE and term GH, but the findings of this case–control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.