New first trimester circulating angiogenic biomarkers in predicting early-onset and late-onset fetal growth restriction: a case-control study.

Background: First trimester prediction of fetal growth restriction (FGR) remain suboptimal. We aimed to search for new circulating angiogenic biomarkers for improvement.

Methods: This case-control study compared 73 singleton pregnancies with early or late-onset FGR based on Delphi consensus and 73 matched normal controls. Their maternal serum samples stored during 11-13 weeks were retrieved for measurement of 36 angiogenic biomarkers by MILLIPLEX^® human angiogenesis magnetic bead panels. Those biomarkers that showed significant differences between the study groups were further analysed with receiver operating characteristic (ROC) curve.

Results: In the early-onset FGR group, log₁₀MoM of soluble neuropilin-1 (sNRP-1: 0.08 ± 0.11 vs. 0.00 ± 0.09, P < 0.001) and log₁₀MoM of soluble platelet and endothelial cell adhesion molecule 1 (sPECAM-1: 0.05 ± 0.06 vs. 0.00 ± 0.09, P < 0.05) were significantly higher than the control group, while log₁₀MoM of platelet-derived growth factor AB/BB (PDGF-AB/BB: -0.08 ± 0.13 vs. 0.00 ± 0.16, P < 0.05) and PAPP-A (-0.15 ± 0.28 vs. 0.05 ± 0.23, P < 0.001) were lower. Their combination achieved the highest area under the ROC curve (AUC) of 0.83 (95% CI: 0.74-0.95) with a higher sensitivity than that of PAPP-A alone (61.5% vs. 30.8% at 10% false positive rate, P < 0.001). Concerning the late-onset FGR group, only log₁₀MoMs of sFlt-1 (-0.12 vs. 0.00, P < 0.001) and PAPP-A (-0.07 vs. 0.05, P < 0.05) were lower than the control group, but their AUC was only 0.68 (95% CI:0.59-0.78).

Conclusions: Three new first trimester biomarkers, sNRP-1, sPECAM-1 and PDGF-AB/BB are predictive of subsequent development of early-onset FGR.