Completed Research

This was a nested case-control study using serum from pregnancies initially screened for PE at 11-13 weeks in a non-interventional study conducted between December 2016 and June 2018, aimed at determining whether maternal levels of glycosylated fibronectin (GlyFn) would increase the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which includes mean arterial pressure, uterine artery pulsatility index, and placental growth factor, for preeclampsia (PE). In this study, serum GlyFn levels were retrospectively measured in 1,792 pregnancies, including 112 with PE, using the Lumella™ enzyme-linked immunoassay (ELISA), and in 448 pregnancies, also including 112 with PE, using the Lumella™ point-of-care device (POC). Concordance between ELISA and POC measured levels was assessed using Lin's correlation and Passing-Bablok (PB) analysis. GlyFn was transformed to multiples of expected median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM levels in PE and non-PE pregnancies, as well as the 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 for preterm PE and any-onset PE was determined from the area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR). Differences in AUC (ΔAUC) between various biomarker combinations were compared using the DeLong test. We found that the concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was 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 with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was significantly elevated in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery in PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE significantly increased the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. In conclusion, replacing PlGF with inhibin-A or adding inhibin-A as an additional biomarker to the FMF triple screening test for preterm and term PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test.