Combined First-Trimester PAPP-A and Free β-hCG Levels for the Early Diagnosis of Placenta Accreta Spectrum and Placenta Previa: A Case-Control Study

Placenta accreta spectrum (PAS) and placenta previa (PP) are severe obstetric disorders associated with high maternal and perinatal morbidity. Early diagnosis of both conditions remains challenging, particularly in cases with subtle imaging findings. This study was aimed to evaluate the diagnostic value of first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG) in predicting PAS and PP. In this retrospective case-control study, a total of 100 pregnant women were included: 36 with PAS, 32 with PP, and 32 healthy controls. Serum levels were measured at 11-13⁶ weeks of gestation. Both biomarkers were significantly altered in pathological groups compared to controls: PAPP-A was lower in PP (3.04 [1.42-4.52] IU/L) and PAS (3.63 [2.51-5.39] IU/L) vs. controls (5.34 [3.72-8.41] IU/L; <i>p</i> < 0.001), while β-hCG was higher in PP (45.4 [40.1-54.9] IU/L) and PAS (51.4 [32.3-74.8] IU/L) vs. controls (33.5 [22.7-54.1] IU/L; <i>p</i> = 0.044 and <i>p</i> < 0.001, respectively). ROC analysis demonstrated that combined biomarker modeling improved diagnostic accuracy over single-marker use, with AUCs reaching 0.85 (sensitivity 85.2%, specificity 72%) for PAS and 0.88 (sensitivity 100%, specificity 72%) for PP. These findings support the integration of biochemical screening into first-trimester risk assessment protocols. Incorporating maternal serum biomarkers may enhance early identification of high-risk pregnancies, allow timely referral to specialized care, and reduce adverse outcomes. Further prospective studies are warranted to validate the utility of this dual-marker approach across diverse populations and clinical settings.