Hidden Signals in Placental Biochemistry: Papp-A Mom as an Early Indicator of Trisomy 21

Purpose: Trisomy 21, or Down Syndrome, is one of the most common chromosomal abnormalities in newborns, appearing in approximately 1 in 700 births, with risk increasing with maternal age. It is a condition of particular importance during firsttrimester screening.

Materials and Methods: We conducted a retrospective cohort study of 2,849 pregnant women at 11+0 and 13+6 weeks of gestation to assess the indicative values of Pregnancy-associated plasma protein-A (PAPP-A) expressed as multiples of the median (MoM), as well as the influence of maternal factors. Differences within groups were made using t-tests or Mann-Whitney U tests for continuous variables, with p < 0.05 considered statistically significant.

Results: Out of the 2,849 pregnant women examined, 293 were classified as high-risk pregnancies (risk for screening in the first trimester ≥ 1:250). We confirmed that PAPP-A MoM values were significantly lower in high-risk pregnancies (median 0.68, IQR 0.4-1.1) compared with the low-risk group (median 1.81, IQR 1.2-2.5; p < 0.0001). Nuchal translucency MoM was slightly lower in high-risk pregnancies (0.87, IQR 0.43-1.20) compared with the low-risk group (0.98, IQR 0.86-1.10; p = 0.0394), while CRL did not differ significantly between groups (70.3 mm vs. 63.1 mm; p = 0.4037).

Conclusions: These findings support the use of combined screening with maternal demographics, ultrasound, and biochemical markers for accurate first-trimester risk assessment. Further studies suggest adjusting MoM values for maternal characteristics to enhance screening performance, reduce false positives, and enable individualized counseling. Early identification is crucial in highrisk pregnancies to facilitate informed decision-making, targeted check-ups, and reinforce the role of integrated, personalized prenatal screening for optimizing maternal and fetal outcomes.