Maternal Serum and Placental Tissue Expression of PLGF and sFlt-1 in Placenta Accreta Spectrum: Correlation With International Federation of Gynecology and Obstetrics (FIGO) Grading of Disease Severity

Introduction: Angiogenesis is a central process in the development of the placenta. This balance between pro-angiogenic and anti-angiogenic factors in the decidua can impact the depth of invasion of the placental villi. This study aimed to understand the relationship between serum PLGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) levels and placental tissue expression of PLGF and sFlt-1 in placenta previa and placenta accreta spectrum (PAS) and to better understand the local and/or systemic role of PLGF and sFlt-1 in the different FIGO PAS grades. Methodology: A case-control study was conducted in the Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, a tertiary care hospital in Northern India, between September 2024 and February 2026. Women with normal placental implantation diagnosed on third trimester ultrasound (USG) were controls, and women with USG showing evidence of placenta previa or PAS were cases. The serum levels of sFlt-1 and PLGF and placenta bed immunohistochemical (IHC) of sFlt-1 and PLGF were analysed between the two groups and between different FIGO grades of PAS. Analysis was done with IBM SPSS Statistics. Results: Fifty women with normal placental implantation (control) and 50 women with placenta previa without invasion or PAS (cases) (placenta previa without invasion -17, FIGO grade 1 PAS-5, grade 2 PAS-12, grade 3 PAS-16) were included in the study. The median age (cases median age = 30, controls = 24, p < 0.001), history of prior caesarean delivery (42 (84%) vs. 6 (12%); p < 0.001) and history of placenta previa in prior pregnancies (21 (42%) vs. 0; p < 0.001) of the cases was significantly higher among the cases as compared to the controls. Serum sFlt-1 (median 5,350 vs. 7,550; p < 0.001) and serum PLGF values (2,550 vs. 5,150, p < 0.001) were lower among cases as compared to controls; there was no difference in the placenta IHC score for sFlt-1 (5 vs. 5; p = 0.770) and PLGF (2 vs. 2; p = 0.106) between groups. In the subgroup analysis of the cases, there was no significant difference between placenta previa without invasion and various grades of PAS with regard to sflt-1, PLGF, sFlt-/PLGF ratio, and placental IHC score for sFlt-1 and PLGF. Conclusion: Angiogenic markers, such as PLGF and sFlt-1, are useful adjunctive biomarkers for identifying abnormal placentation. However, their role is limited to detection rather than grading of PAS.