Glycosylated fibronectin improves first trimester prediction of pre‐eclampsia

Objective

To determine whether maternal levels of glycosylated fibronectin (GlyFn) would increase the sensitivity of the Fetal Medicine Foundation (FMF) triple test with mean arterial pressure, uterine artery pulsatility index and placental growth factor for preeclampsia (PE) in Asian population.

Methods

This is a nested case‐control study using serum from Chinese women having a singleton pregnancy initially screened for PE at 11‐13 weeks in a non‐intervention study conducted between December 2016 and June 2018. Serum GlyFn levels were retrospectively measured in 1792 pregnancies, including 112 with PE, using the Lumella^TM enzyme‐linked immunoassay (ELISA) and in 448 pregnancies, including 112 with PE, using the Lumella^TM point‐of‐care (POC) device. Concordance between ELISA and POC measured levels was assessed using Lins correlation and Passing‐Bablok (PB) analysis. GlyFn was transformed to multiples of expected median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM in PE and non‐PE pregnancies and association between GlyFn MoM and gestational age at delivery in PE were assessed. Risks for PE were estimated using the FMF competing risk model. The screening performance, preterm PE and any‐onset PE were determined from area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR). Differences in AUC (ΔAUC) between different biomarker combinations were compared using the Delong test.

Results

Concordance correlation between ELSIA and POC measurements was 0.86 (95% confidence interval [CI]: 0.83–0.88). PB analysis indicated proportional bias (slope=1.08;95%CI: 1.04‐1.14) with POC GlyFn being significantly higher than ELISA. GlyFn levels in non‐PE pregnancies were independent of gestational age at screening (p>0.11) but significantly dependent on maternal age (p<0.003), weight(p<0.0002), height (p=0.001), parity (p<0.02), and smoking status (p=0.002). Compared to non‐PE pregnancies, mean ELISA and POC GlyFn MoM levels in preterm PE (1.23 vs 1.00; p<0.0001 and 1.18 vs 1.00; p<0.0001 respectively) and term PE (1.26 vs 1.00; p<0.0001 and 1.22 vs 1.00; p<0.0001 respectively) pregnancies were significantly increased. GlyFn MoM was not significantly correlated with gestational age at delivery (p=0.989). Adding GlyFn to the FMF triple test for preterm PE screening significantly increased AUC from 0.859 to 0.896 (ΔAUC=0.037; p=0.012) and increased DR from 64.86% (95%CI: 48.65%‐81.08%) to 82.86% (95%CI: 66.35%‐93.44%) for a 10% FPR. At the same FPR, DR increased from 52.48% (95%CI: 42.30% – 62.51%) to 65.35% (95%CI: 55.23% – 74.54%) when screening for any‐onset PE by adding GlyFn.

Conclusion

Adding GlyFn has increased screening sensitivity of the FMF triple test for both preterm and any‐onset PE in Asian population. Prospective non‐intervention studies are needed to confirm our initial findings.

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