Correlations Between Pregnancy-Associated Plasma Protein A Levels and Pregnancy Characteristics, Placental Volume, Vascularization, and Histopathology

Abstract Objective: To evaluate the associations between pregnancy-associated plasma protein A (PAPP-A) levels and pregnancy-associated conditions, perinatal outcomes, and placental histopathology. Methods: This retrospective, single-center cohort analysis included cases of preterm and term deliveries from pregnancies complicated by preeclampsia and fetal growth restriction or gestational hypertension. A correlation analysis was performed to assess the relationship between PAPP-A levels and neonatal parameters, the prevalence of various pregnancy complications, and placental and birth weight percentiles and ratios. Associations between placental histopathological entities and PAPP-A were explored in different subgroups defined by PAPP-A multiple of the median (MoM) ranges. Potential associations between PAPP-A levels and placental capillarization were also investigated. Results: A total of 74 pregnancies were investigated. PAPP-A levels were significantly lower in cases involving cesarean section ( P = 0.002), preterm birth ( P = 0.030), and/or preeclampsia ( P = 0.002). Among the preeclamptic cases, early-onset preeclampsia was associated with a significantly lower PAPP-A level ( P < 0.001). No significant associations were identified between first-trimester PAPP-A levels and placental weight percentile, birth weight percentile, villous capillarization, or the percentage of intact terminal villi; however, correlations were found between low PAPP-A levels and placental weight-to-birth weight ratios of < 1:8 (Kruskal–Wallis test P = 0.004; Spearman’s correlation P = 0.011). PAPP-A levels were also significantly lower in the presence of distal villous hypoplasia ( P < 0.001), accelerated villous maturation ( P < 0.001), or avascular villi ( P < 0.001) in the placenta. Conclusion: Lower PAPP-A levels may represent an early marker of pathological placentation in the background of preeclampsia and fetal growth restriction—especially in early-onset cases—which are characterized by villous underdevelopment and a non-branching villous tree pattern on placental histopathology. From a clinical translation perspective, PAPP-A levels may serve as a potential early indicator of pregnancies that warrant close monitoring during clinical management.