Osteopontin levels in maternal serum and placenta: Associations with fetal growth restriction and neonatal outcomes

Abstract Objective To investigate maternal serum and placental osteopontin levels in pregnancies complicated with fetal growth restriction (FGR) and to evaluate their association with composite adverse neonatal outcomes (CANO). Methods A prospective case‐control study was conducted at Etlik City Hospital between March and September 2024, including 40 women with pregnancies affected by FGR (34–39 weeks) and 40 gestational age‐matched healthy control women. FGR was diagnosed using Delphi criteria. Maternal venous blood and placental samples were collected at delivery. Serum and placental osteopontin levels were measured using enzyme‐linked immunosorbent assay. Placental osteopontin concentrations were normalized to total protein by the Bradford method (ng/mg protein). Statistical analyses included Mann–Whitney U , χ 2 , and Fisher exact tests, and receiver operating characteristic (ROC) analysis. Results A total of 80 participants were analyzed. Gravidity and parity were lower in the FGR group, whereas maternal age and body mass index were comparable. As expected, adverse perinatal outcomes were more frequent in the FGR group. Both maternal serum and placental osteopontin levels were significantly decreased in FGR cases compared with controls ( P = 0.002 and P < 0.001, respectively). ROC analysis demonstrated the best predictive performance for placental osteopontin normalized to total protein, with a cut‐off of 61.2 ng/mg (area under the curve AUC 0.791, sensitivity 77.5%, specificity 70.0%). Lower osteopontin levels were also predictive of CANO (AUC up to 0.760, P < 0.001). Conclusions In pregnancies complicated by FGR, osteopontin levels were significantly reduced in both maternal serum and placental tissue. This decrease may reflect impaired spiral artery remodeling and placental angiogenesis, contributing to the molecular mechanisms of placental insufficiency and adverse neonatal outcomes.