ELEVATED SERUM OSTEOPONTIN IN WOMEN WITH A HISTORY OF RECURRENT MISCARRIAGE: AN ANALYTICAL CASE–CONTROL STUDY

Background: Recurrent miscarriage (RM) affects 2–6% of couples attempting to conceive and remains unexplained in nearly half of affected women despite extensive investigation. Osteopontin (OPN), a multifunctional secreted glycoprotein required for endometrial decidualization and angiogenesis, has been proposed as a peripheral marker of the maternal fetal interface pathology underlying RM, but its diagnostic value has not been fully established. Objective: To measure and compare serum osteopontin levels between women with a history of recurrent miscarriage and healthy fertile controls, and to explore the association between serum OPN and a history of RM. Methodology: An analytical case–control study was conducted on 44 women with a history of ≥2 pregnancy losses before 20–24 weeks of gestation (RM group) and 42 healthy fertile women with no history of miscarriage (control group), recruited at the Maternity and Children Hospital, Basra, Iraq (October 2025–February 2026). Serum OPN was measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was used descriptively to quantify the separation between the two predefined groups. Results: The two groups were well matched for age (p = 0.271) and body mass index (p = 0.941). Serum OPN was significantly higher in the RM group (mean 4.57 ± 3.66 ng/mL; median 3.26 ng/mL; range 0.69–16.35 ng/mL) than in controls (mean 1.71 ± 2.07 ng/mL; median 0.91 ng/mL; range 0.02–10.74 ng/mL; p < 0.001). ROC analysis showed an area under the curve (AUC) of 0.82; at the exploratory Youden-derived cutoff of 1.083 ng/mL, 97.7% of RM participants and 61.9% of controls were correctly classified within this same sample. OPN showed no significant correlation with BMI. Conclusion: Serum OPN is significantly and substantially elevated in non-pregnant women with a history of recurrent miscarriage relative to healthy fertile controls. Together with its mechanistic role in decidual and vascular remodeling, these findings identify OPN as a biologically plausible candidate for further investigation. The present case–control design cannot establish diagnostic, predictive, or screening utility, and prospective validation in larger, longitudinal cohorts is required.