Association between placenta accreta spectrum and third-trimester serum levels of vascular endothelial growth factor, placental growth factor, and soluble Fms-like tyrosine kinase-1: A meta-analysis.

Aim: Antenatal suspicion of placenta accreta spectrum (PAS) currently relies on ultrasonographic findings, color doppler, and MRI, which have rendered it operator and expertise-dependent. No serum markers for PAS have been integrated into clinical practice yet. The aim of this meta-analysis was to identify potential serum markers for PAS by investigating third-trimester serum levels of vascular endothelial growth factor (VEFG), placental growth factor (PIGF), and soluble Fms-like tyrosine kinase-1 (sFlt-1) among PAS-cases and controls.

Methods: PubMed, Scopus, EBSCO, Web of Science, and CNKI databases were systematically searched for relevant articles. Random-effects model was applied to calculate the overall standardized mean difference (SMD) for each marker. Subgroup analysis and meta-regression were performed to assess for potential covariates.

Results: Eight studies involving 366 PAS-cases and 518 controls were included. Third trimester sFlt-1 levels were significantly lower in PAS-cases when compared to controls (SMD = -7.76, 95%CI = -10.42 to -5.10). This was, to a certain extent, consistent among studies though they differed in their extent of significance. Levels of VEGF (SMD = 1.59, 95%CI = -0.07 to 3.25) and PlGF (SMD = -0.49, 95%CI = -1.66 to 0.67) were not significantly different between PAS cases and controls, in which studies demonstrated conflicting results.

Conclusions: Third trimester sFlt-1 levels may be useful to predict PAS. Nonetheless, further studies are recommended to better understand conflicting results before adopting either VEGF or PlGF.