Background: Maternal serum biomarkers, primarily introduced for aneuploidy screening, have also been investigated as predictors of adverse pregnancy outcomes. However, their value in late-preterm and term pregnancies remains unclear.
Methods: In this retrospective cohort study, 592 singleton pregnancies screened at a tertiary perinatology center between 2020 and 2025 were analyzed. Participants underwent either the first-trimester combined test (n = 461) or the second-trimester triple test (n = 131). Serum biomarker multiples of the median (MoM) were categorized as low (< 0.5), normal (0.5-2.0), or high (> 2.0). Perinatal outcomes-including Apgar scores, umbilical artery pH, neonatal intensive care unit (NICU) admission, and preterm premature rupture of membranes (PPROM)-were assessed using predefined group comparisons, multivariate adjustment, and ROC curve analysis.
Results: Low first-trimester free β-hCG was significantly associated with reduced Apgar scores at 1 and 5 min in term neonates (p = 0.025 and p = 0.005, respectively). In the second trimester, infants with normal AFP levels demonstrated lower umbilical artery pH compared to those with elevated AFP (p = 0.013), and low AFP was associated with an increased risk of NICU admission (p = 0.041). ROC analysis identified an AFP threshold ≥ 1.075 MoM as predictive of PPROM with 75.0% sensitivity and 69.3% specificity (AUC = 0.723, p = 0.035). No significant associations were observed for PAPP-A.
Conclusions: First-trimester low free β-hCG and second-trimester AFP abnormalities showed modest associations with neonatal outcomes and PPROM in late-preterm and term pregnancies, whereas PAPP-A did not. These findings suggest limited standalone predictive capacity of serum biomarkers, underscoring the need for integrated multiparametric models in risk stratification.
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