Prospective Evaluation of Maternal Serum sFlt-1, PlGF, and the sFlt- 1/PlGF Ratio in Placenta Accreta Spectrum and Their Correlation With Placental Immunohistochemical Expression

Abstract Background Placenta accreta spectrum (PAS) is associated with substantial maternal morbidity and mortality, particularly because of severe obstetric haemorrhage. Although antenatal imaging remains the cornerstone of diagnosis, additional biomarkers may have potential value, particularly where access to advanced imaging is limited. This study evaluated maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio in women with PAS and examined their relationship with placental immunohistochemical expression. Methods This prospective case–control study was conducted at Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, in collaboration with the ICMR–National Institute of Pathology. Women with singleton pregnancies beyond 28 weeks with confirmed or clinically diagnosed PAS were enrolled as cases, while age- and gravidity-matched women undergoing caesarean delivery without PAS served as controls. Maternal plasma sFlt-1 and PlGF concentrations were measured using enzyme-linked immunosorbent assays. Placental tissue was evaluated by histopathology and immunohistochemistry for sFlt-1 and PlGF. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis, and multivariable logistic regression was performed to account for baseline clinical differences. Results Sixty women were included in the final analysis, comprising 40 PAS cases and 20 controls. Median plasma sFlt-1 concentrations were lower in PAS cases than controls (23.5 vs. 29.8 ng/mL; p = 0.034), whereas PlGF concentrations were higher (270.5 vs. 48.2 pg/mL; p = 0.006). The median sFlt-1/PlGF ratio was significantly lower in PAS cases (88.1 vs. 561.1; p = 0.001). ROC analysis demonstrated an area under the curve (AUC) of 0.670 for sFlt-1, 0.716 for PlGF, and 0.753 for the sFlt-1/PlGF ratio. At the selected cut-offs, sFlt-1 showed 100% sensitivity and 65% specificity, PlGF showed 62.5% sensitivity and 100% specificity, and the sFlt-1/PlGF ratio showed 62.5% sensitivity and 95% specificity. None of the three biomarkers differed significantly according to histopathological depth of invasion. In multivariable logistic regression, the sFlt-1/PlGF ratio was not independently associated with PAS after adjustment for maternal age, parity, previous caesarean delivery, and previous placenta previa ( p = 0.110). Placental PlGF immunohistochemical expression showed a significant positive association with plasma PlGF concentration ( p < 0.001), whereas sFlt-1 tissue expression was uniformly weak. Conclusions Maternal plasma sFlt-1, PlGF, and the sFlt-1/PlGF ratio were significantly different in women with PAS compared with controls and demonstrated moderate discriminatory performance. The sFlt-1/PlGF ratio showed the highest AUC among the biomarkers evaluated; however, it was not independently associated with PAS after adjustment for clinical factors. Plasma PlGF correlated significantly with placental PlGF immunohistochemical expression, supporting a biological relationship between circulating and placental PlGF. Larger prospective studies are required to determine whether these biomarkers can provide clinically useful adjunctive information for PAS screening and diagnosis.