First-trimester PAPP-A, free β-hCG, and nuchal translucency for predicting fetal growth restriction

Background: Early identification of pregnancies at risk for fetal growth restriction (FGR) is essential for appropriate prenatal monitoring and timely intervention. First-trimester screening markers, including nuchal translucency (NT), pregnancy-associated plasma protein A (PAPP-A), and free β-human chorionic gonadotropin (free β-hCG), are routinely used in clinical practice and may provide early insight into placental function. Methods: This cohort study analysed first-trimester biochemical and ultrasound markers in pregnancies that later developed FGR and compared them with those of uncomplicated control pregnancies. NT was measured between 11 and 13+6 gestational weeks, while PAPP-A and free β-hCG concentrations were expressed as multiples of the median (MoM). Correlation analyses and logistic regression models were applied to evaluate associations and predictive value. Results: NT values were significantly higher in pregnancies complicated by FGR. Mean PAPP-A and free β-hCG levels did not differ significantly between the FGR and control groups. Correlations among first-trimester markers were more consistent in the control group, whereas disrupted relationships were observed in FGR pregnancies. Although mean PAPP-A values were similar, very low PAPP-A levels (<5th percentile) were associated with an increased risk of FGR. The combined presence of elevated NT and low PAPP-A improved the identification of high-risk pregnancies. Conclusion: NT may serve as a potential early indicator of FGR risk, particularly when interpreted within specific clinical sub-stratifications rather than as a standalone screening tool. Extremely low PAPP-A values may further contribute to early risk stratification. The combined interpretation of biochemical and sonographic markers in the first trimester may support earlier identification of pregnancies requiring closer surveillance.