Combined prognostic value of first-trimester PAPP-A, placental volume and sFlt-1/PlGF ratio for early prediction of fetal growth restriction
Keywords:
Fetal growth restriction, PAPP-A, sFlt-1/PlGF ratio, placental volume, first trimester, placental dysfunction, biomarkersAbstract
Background and Aim: This study aimed to evaluate the individual and combined prognostic value of first-trimester placental biomarkers, including PAPP-A, the sFlt-1/PlGF ratio, and placental volume calculated using the Harvey J. Kliman method, for early prediction of fetal growth restriction (FGR). Methods: This retrospective analytical cohort study included 50 women with singleton pregnancies and known delivery outcomes. The study was approved by the local ethics committee and conducted in accordance with the Declaration of Helsinki. Birth weight percentiles were calculated according to gestational age and fetal sex using the INTERGROWTH-21st standards. FGR was defined as birth weight below the 10th percentile. First-trimester PAPP-A (MoM), sFlt-1/PlGF ratio, and ultrasound-based placental volume were analyzed. Diagnostic performance was assessed using ROC curve analysis, and optimal cut-off values were determined using the Youden index. Multivariate logistic regression was performed to evaluate independent and combined predictive effects. Results: FGR was identified in 8 cases (16%); one intrauterine fetal death occurred. PAPP-A demonstrated high predictive performance (AUC = 0.842), while the sFlt-1/PlGF ratio showed moderate accuracy (AUC = 0.771). Placental volume had limited predictive value (AUC = 0.574). Optimal cut-offs were PAPP-A ≤ 0.69 MoM, sFlt-1/PlGF ≥ 122, and placental volume ≤ 74 cc. The combined biomarker model improved overall predictive performance (AUC = 0.807). Conclusions: Low first-trimester PAPP-A was the strongest early predictor of FGR. Combined assessment of biochemical and morphological placental markers improved diagnostic accuracy and may support early risk stratification in clinical practice.
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