Predictive Performance of Simplified First-Trimester Placental Volume Estimation Combined with Uterine Artery Doppler and Maternal Serum Biomarkers for Preeclampsia and Fetal Growth Restriction: A Retrospective Cohort Study

Background: Preeclampsia and fetal growth restriction (FGR) are major obstetric complications originating from abnormal placental development during early pregnancy. Early identification of pregnancies at increased risk remains challenging despite the availability of several first-trimester biochemical and biophysical markers. Objective: This study aimed to evaluate the predictive value of first-trimester placental volume, bilateral uterine artery Doppler pulsatility indices (UtA-PI), pregnancy-associated plasma protein-A (PAPP-A), and free β-human chorionic gonadotropin (free β-hCG) for the subsequent development of preeclampsia and FGR. Methods: This retrospective cohort study included 251 singleton pregnancies that underwent routine first-trimester aneuploidy screening. Placental volume was estimated using a standardized two-dimensional ultrasonographic method; bilateral uterine artery Doppler examinations were performed according to Fetal Medicine Foundation recommendations, and maternal serum PAPP-A and free β-hCG values were recorded as multiples of the median. Receiver operating characteristic (ROC) analysis, multivariable logistic regression, and leave-one-out cross-validation were performed to evaluate predictive performance. Results: Preeclampsia and FGR developed in 8 (3.2%) and 29 (11.6%) pregnancies, respectively. None of the investigated biochemical or biophysical markers differed significantly between affected and unaffected pregnancies. Individual biomarkers demonstrated poor discriminatory performance, with AUC values ranging from 0.50 to 0.64. Following adjustment for maternal characteristics, only lower maternal free β-hCG remained independently associated with FGR (adjusted OR 0.49, 95% CI 0.25–0.96; p = 0.038). The apparent performance of the combined prediction model was not maintained following internal validation, indicating substantial model overfitting. Conclusions: First-trimester placental volume, uterine artery Doppler indices, PAPP-A, and free β-hCG demonstrated limited predictive performance for preeclampsia and FGR in this cohort. These findings suggest that currently available first-trimester biomarkers are insufficient as stand-alone screening tools and support the development of multimodal prediction strategies integrating biochemical, biophysical, angiogenic, and molecular biomarkers rather than relying on isolated first-trimester markers.