Maternal serum thrombospondin-4 levels in placenta accreta spectrum: A case-control study

This study evaluates maternal serum thrombospondin-4 (TSP-4) levels in pregnancies complicated by placenta accreta spectrum (PAS) and examine their association with maternal and neonatal outcomes.

This prospective case-control study included 80 pregnancies, comprising 40 cases with PAS and 40 healthy controls. The study was conducted at Ankara Etlik City Hospital between June 2025 and March 2026. Maternal serum TSP-4 levels were measured by ELISA. Clinical, obstetric, maternal, and neonatal data were recorded. Univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed, including comparison of a clinical model with and without TSP-4.

Maternal serum TSP-4 levels were significantly higher in the PAS group than in controls (9.88 [9.38-10.00] vs. 7.83 [6.01-9.30] ng/mL; P < 0.001). PAS was associated with prolonged hospitalization, increased transfusion requirement, earlier delivery, lower birth weight, lower Apgar scores, higher neonatal intensive care unit admission rates, and increased rates of adverse maternal and neonatal composite outcomes. Within the PAS cohort, TSP-4 levels were not associated with composite adverse maternal outcome, PAS grade, or major neonatal outcomes. In multivariable analysis, TSP-4 was the only variable independently associated with PAS (adjusted odds ratio 1.863, 95% confidnece interval [CI] 1.308-2.651; P = 0.001). ROC analysis demonstrated moderate discriminative ability (area under the curve [AUC] 0.796, 95% CI 0.697-0.895). At a cutoff value of >9.47 ng/mL, sensitivity and specificity were 72.5% and 82.5%, respectively, yielding a positive likelihood ratio of 4.14 and a negative likelihood ratio of 0.33. Adding TSP-4 to the clinical model increased the AUC from 0.660 to 0.816 (P = 0.002 for the difference).

Maternal serum TSP-4 is elevated in PAS and, by adding discriminative value to clinical predictors, might be considered a complementary biomarker candidate for antenatal risk stratification, although these associations warrant confirmation in larger, prospective, multicenter cohorts. Its value appears greater for identifying disease presence than for reflecting disease severity.